Search

Background: To evaluate a novel intraoperative localization technique utilizing temporary pulmonary arteriovenous occlusion for enhancing the precision of sublobar resections in early-stage NSCLC., Methods: Conducted from January to November 2023, this study involved 140 patients. During the surgery, key pulmonary vessels were identified using preoperative three-dimensional (3D) imaging and temporarily occluded with noninvasive clamps to isolate the target lung segment. Following vascular occlusion, indocyanine green (ICG) was administered intravenously to precisely delineate the resection margins. After visually confirming the marked areas, the clamps were released, and a targeted partial resection was performed on the delineated segment. Surgical data, including operation times, surgical margins, and hospitalization costs, were collected and compared with those from a historical control group of 110 patients who underwent traditional pulmonary wedge resections., Results: In the study group, the median surgical margin achieved was 16 mm, which was statistically significant compared to 15 mm in the control group (p < 0.05). Operation times were reduced to an average of 58.43 ± 12.962 min, showing a decrease from the control group's average of 69.50 ± 17.544 min (p < 0.05). Hospitalization costs were also lower, averaging $4772.98 ± 624.339 for the study group versus $5161.34 ± 856.336 for the control group (p < 0.05). Patient safety was maintained with no increase in surgical complications., Conclusion: The technique, leveraging temporary pulmonary arteriovenous occlusion, offered a significant advancement in the surgical treatment of peripheral early-stage NSCLC. It reduced operation time and lowered overall surgical costs. This method represented a promising alternative to traditional surgical approaches., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: BRAF inhibitors are approved in BRAF V600 -mutated metastatic melanoma, non-small-cell lung cancer (NSCLC), Erdheim-Chester disease (ECD), and thyroid cancer. We report here the efficacy, safety, and long-term results of single-agent vemurafenib given in the AcSé vemurafenib basket study to patients with various BRAF-mutated advanced tumours other than BRAF V600 -mutated melanoma and NSCLC., Patients and Methods: Patients with advanced tumours other than BRAF V600E melanoma and progressing after standard treatment were eligible for inclusion in nine cohorts (including a miscellaneous cohort) and received oral vemurafenib 960 mg two times daily. The primary endpoint was the objective response rate (ORR) estimated with a Bayesian design. The secondary outcomes were disease control rate, duration of response, progression-free survival (PFS), overall survival (OS), and vemurafenib safety., Results: A total of 98 advanced patients with various solid or haematological cancers, 88 with BRAF V600 mutations and 10 with BRAF nonV600 mutations, were included. The median follow-up duration was 47.7 months. The Bayesian estimate of ORR was 89.7% in hairy cell leukaemias (HCLs), 33.3% in the glioblastomas cohort, 18.2% in cholangiocarcinomas, 80.0% in ECD, 50.0% in ovarian cancers, 50.0% in xanthoastrocytomas, 66.7% in gangliogliomas, and 60.0% in sarcomas. The median PFS of the whole series was 8.8 months. The 12-, 24-, and 36-month PFS rates were 42.2%, 23.8%, and 17.9%, respectively. Overall, 54 patients died with a median OS of 25.9 months, with a projected 4-year OS of 40%. Adverse events were similar to those previously reported with vemurafenib., Conclusion: Responses and prolonged PFS were observed in many tumours with BRAF mutations, including HCL, ECD, ovarian carcinoma, gliomas, ganglioglioma, and sarcomas. Although not all cancer types responded, vemurafenib is an agnostic oncogene therapy of cancers., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did not progress after six to eight cycles of chemotherapy. Patients (n = 199) were randomized to either durvalumab (10 mg kg -1 every 2 weeks) or maintenance chemotherapy. In the overall population, durvalumab did not improve progression-free survival (adjusted hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.00-1.96; P = 0.047) or overall survival (OS; adjusted HR: 0.84, 95% CI: 0.54-1.29; P = 0.423). In an exploratory subgroup analysis, durvalumab improved OS in patients with triple-negative breast cancer (TNBC; n = 82; HR: 0.54, 95% CI: 0.30-0.97, P = 0.0377). Exploratory analysis showed that the HR of death was 0.37 (95% CI: 0.12-1.13) for patients with PD-L1 + TNBC (n = 32) and 0.49 (95% CI: 0.18-1.34) for those with PD-L1 - TNBC (n = 29). In patients with TNBC, exploratory analyses showed that the HR for durvalumab efficacy (OS) was 0.18 (95% CI: 0.05-0.71; log-rank test, P = 0.0059) in patients with CD274 gain/amplification (n = 23) and 1.12 (95% CI: 0.42-2.99; log-rank test, P = 0.8139) in patients with CD274 normal/loss (n = 32). Tumor infiltration by lymphocytes (CD8, FoxP3 and CD103 expressions) and homologous recombination deficiency did not predict sensitivity to durvalumab in exploratory analyses. This latter finding should be interpreted with caution since only one patient presented a germline BRCA mutation. The present study provides a rationale to evaluate single-agent durvalumab in maintenance therapy in patients with TNBC. Exploratory analyses identified CD274 amplification as a potential biomarker of sensitivity. Maintenance chemotherapy was more effective than durvalumab in patients with hormone receptor-positive and Her2-negative disease.

Cell membrane- covered drug-delivery nanoplatforms have been garnering attention because of their enhanced bio-interfacing capabilities that originate from source cells. In this top-down technique, nanoparticles (NPs) are covered by various membrane coatings, including membranes from specialized cells or hybrid membranes that combine the capacities of different types of cell membranes. Here, hybrid membrane-coated doxorubicin (Dox)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs (DPLGA@[RAW-4T1] NPs) were fabricated by fusing membrane components derived from RAW264.7(RAW) and 4T1 cells (4T1). These NPs were used to treat lung metastases originating from breast cancer. This study indicates that the coupling of NPs with a hybrid membrane derived from macrophage and cancer cells has several advantages, such as the tendency to accumulate at sites of inflammation, ability to target specific metastasis, homogenous tumor targeting abilities in vitro, and markedly enhanced multi-target capability in a lung metastasis model in vivo. The DPLGA@[RAW-4T1] NPs exhibited excellent chemotherapeutic potential with approximately 88.9% anti-metastasis efficacy following treatment of breast cancer-derived lung metastases. These NPs were robust and displayed the multi-targeting abilities of hybrid membranes. This study provides a promising biomimetic nanoplatform for effective treatment of breast cancer metastasis.

Artificial intelligence (AI) based on deep learning, convolutional neural networks and big data has been increasingly effective in the diagnosis and treatment of multiple primary pulmonary nodules. In comparison to previous imaging systems, AI measures more objective parameters such as three-dimensional (3D) volume, probability of malignant nodules, and possible pathological patterns, making the access to the properties of nodules more objective. In our retrospective study, a total of 53 patients with synchronous and metachronous multiple pulmonary nodules were enrolled of which 33 patients were confirmed by pathological tests to have primary binodules, and nine to have primary trinodules. A total of 15 patients had only one focus removed. The statistical results showed that the agreement in the AI diagnosis and postoperative pathological tests was 88.8% in identifying benign or malignant lesions. In addition, the probability of malignancy of benign lesions, preinvasive lesions (AAH, AIS) and invasive lesions (MIA, IA) was totally different (49.40±38.41% vs 80.22±13.55% vs 88.17±17.31%). The purpose of our study was to provide references for the future application of AI in the diagnosis and follow-up of multiple pulmonary nodules. AI may represent a relevant diagnostic aid that shows more accurate and objective results in the diagnosis of multiple pulmonary nodules, reducing the time required for interpretation of results by directly displaying visual information to doctors and patients and together with the clinical conditions of MPLC patients, offering plans for follow-up and treatment that may be more beneficial and reasonable for patients. Despite the great application potential in pneumosurgery, further research is needed to verify the accuracy and range of the application of AI., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objective: This study aimed to assess the outcome of first-line hysterectomy in patients diagnosed as having gestational trophoblastic neoplasia (GTN) whose postoperative imaging showed lung images considered as metastases., Methods: From 1999 to 2016, patients no longer wishing to conceive, treated by their initial physician by hysterectomy, and whose postoperative imaging workup showed lung images considered as metastasis were identified in the French Trophoblastic Disease Reference Center database. We sought to identify significant predictive factors of requiring salvage chemotherapy., Results: Thirty patients were identified with a maximum number of 2 visible lung nodules and a median largest size of 14 mm on chest x-ray. Nine of these patients had an International Federation of Gynecology and Obstetrics score of higher than 6, and there were no postterm GTN. Twenty-two patients (73.33%; 95% confidence interval, 54.11-87.72; P = 0.0053) normalized their human chorionic gonadotropin (hCG) without salvage chemotherapy, whereas 7 received 1 line of salvage monochemotherapy (8-day methotrexate) and 1 required 2 lines of monochemotherapy (5-day actinomycin D after failure of methotrexate). After a 12.45-month median follow-up (range, 3-48.4 months) since the first normalized hCG, none of these patients died. The median interval between successful hysterectomy and hCG normalization was 3.15 months (range, 1.6-8.7 months). Patients who required salvage chemotherapy had a median size of the largest lung metastasis on chest computed tomography of 4 mm larger than those cured by hysterectomy (P = 0.0455)., Conclusions: For GTN patients no longer wishing to conceive with lung metastases discovered postoperatively, treated by hysterectomy, and whose hCG is decreasing, it is reasonable to expect and to inform patients that approximately 27% will require salvage chemotherapy. However, in patients with lung metastases discovered preoperatively, evidence to recommend first-line hysterectomy is insufficient and these patients should receive first-line chemotherapy.

Drug development involves various evaluation processes to ascertain drug effects and rigorous analysis of biological indicators during in vitro preclinical studies. Two-dimensional (2D) cell cultures are commonly used in numerous in vitro studies, which are poor facsimiles of the in vivo conditions. Recently, three-dimensional (3D) tumor models mimicking the tumor microenvironment and reducing the use of experimental animals have been developed generating great interest to appraise tumor response to treatment strategies in cancer therapy. In this study, silk fibroin (SF) protein and chitosan (CS), two natural biomaterials, were chosen to construct the scaffolds of 3D cell models. Human non-small cell lung cancer A549 cells in the SF/CS scaffolds were found to have a great tendency to gather and form tumor spheres. A549 cell spheres in the 3D scaffolds showed biological and morphological characteristics much closer to the in vivo tumors. Besides, the cells in 3D models displayed better invasion ability and drug resistance than 2D models. Additionally, differences in drug-resistant and immune-related protein levels were found, which indicated that 3D models might resemble the real-life situation. These findings suggested that these 3D tumor models composed of SF/CS are promising to provide a valuable biomaterial platform in the evaluation of anticancer drugs.

Objective: To investigate the current status of prevention and treatment of venous thromboembolism (VTE) after thoracic surgery in China. Method: Chinese thoracic surgeons were investigated by the online questionnaire which was based on the Chinese version of International VTE questionnaire added with 6 extra questions with Chinese characteristics. Results: A total of 1 150 valid questionnaires were retrieved, accounting for about 20% of all the Chinese thoracic surgeons. The surgeons participating in this survey came from all over the country, most of whom were experienced professionals with high academic titles.For lung cancer patients, 66.96% (770/1 150) of the surgeons suggested that VTE prophylaxis should start 1 day after lung cancer resection, and 64.61% (743/1 150) of the surgeons suggested extending after discharge. For esophagestomy patients, and 48.35% (514/1 063) of the surgeons suggested that there was no need for patients to extend VTE prophylaxis after discharge. More than half of the surgeons participating in this survey made decision of the method and duration of VTE prophylaxis after lung cancer resection (53.91% (620/1 150)) or esophagectomy (52.49% (558/1 063)) depending on the clinical experience.Low molecular weight heparin was the common choice of most surgeons in VTE prophylaxis. More than half of the surgeons thought that previous history of VTE, advanced age, complicated with thrombophilia, obesity (body mass index>30 kg/m 2 ), duration of surgery longer than 6 hours and family history of VTE were key risk factors of the occurrence of postoperative VTE. Conclusions: The results of this survey are highly credible and are a good reflection of the current status of VTE prevention and treatment after thoracic surgery in China. This survey will play an important role in promoting VTE prevention and treatment in Chinese thoracic surgery department, it will also provide data support for government setting new policies, hospital construction of VTE prevention and control as well as raising physicians' awareness.

Yes-associated protein (YAP) is a main mediator of the Hippo pathway, which promotes cancer development. Here we show that YAP promotes resistance to erlotinib in human non-small cell lung cancer (NSCLC) cells. We found that forced YAP overexpression through YAP plasmid transfection promotes erlotinib resistance in HCC827 (exon 19 deletion) cells. In YAP plasmid-transfected HCC827 cells, GTIIC reporter activity and Hippo downstream gene expression of AREG and CTGF increased significantly (P<0.05), as did ERBB3 mRNA expression (P<0.05). GTIIC reporter activity, ERBB3 protein and mRNA expression all increased in HCC827 erlotinib-resistance (ER) cells compared to parental HCC827 cells. Inhibition of YAP by small interfering RNA (siRNA) increased the cytotoxicity of erlotinib to H1975 (L858R+T790M) cells. In YAP siRNA-transfected H1975 cells, GTIIC reporter activity and downstream gene expression of AREG and CTGF decreased significantly (P<0.05). Verteporfin, YAP inhibitor had an effect similar to that of YAP siRNA; it increased sensitivity of H1975 cells to erlotinib and in combination with erlotinib, synergistically reduced migration, invasion and tumor sphere formation abilities in H1975 cells. Our results indicate that YAP promotes erlotinib resistance in the erlotinib-sensitive NSCLC cell line HCC827. Inhibition of YAP by siRNA increases sensitivity of erlotinib-resistant NSCLC cell line H1975 to erlotinib., Competing Interests: CONFLICTS OF INTERESTS All authors have no conflicts of interest.

Objective: To investigate the impact of coal workers' pneumoconiosis complicated by the pathological changes in lymph nodes in lung cancer on surgical treatment., Methods: A total of 63 patients with non-small cell lung cancer who received pulmonary lobectomy and systemic mediastinal lymph node dissection were enrolled and divided into the group with coal workers' pneumoconiosis complicated by lung cancer (30 patients) and the non-pneumoconiosis liver cancer group (33 patients). The short-term outcome was compared between the two groups and confirmed by lymph node fibrosis shown by postoperative pathological examination. The predictive value of lymphadenectasis on chest CT was analyzed., Results: Compared with the non-pneumoconiosis liver cancer group, the group with coal workers' pneumoconiosis complicated by lung cancer had significant increases in time of operation, intraoperative blood loss, postoperative extubation time, and length of hospital stay (P<0.05). The patients were divided into groups according to the presence or absence of lymph node fibrosis, and the group with lymph node fibrosis had a significantly longer time of operation and greater intraoperative blood loss than the group without lymph node fibrosis (P<0.05)., Conclusion: When coal workers' pneumoconiosis is complicated by lung cancer, severe lymph node fibrosis often causes difficulties in surgery, and thoracotomy may be a safe and effective therapeutic method.

Alterations of the EGFR/ERK and Hippo/YAP pathway have been found in non-small cell lung cancer (NSCLC). Herein, we show that ERK1 and ERK2 have an effect on the Hippo/YAP pathway in human NSCLC cells. Firstly, inhibition of ERK1/2 by siRNA or small-molecular inhibitors decreased the YAP protein level, the reporter activity of the Hippo pathway, and the mRNA levels of the Hippo downstream genes, CTGF, Gli2, and BIRC5. Secondly, degradation of YAP protein was accelerated after ERK1/2 depletion in NSCLC cell lines, in which YAP mRNA level was not decreased. Thirdly, forced over-expression of the ERK2 gene rescued the YAP protein level and Hippo reporter activity after siRNA knockdown targeting 3'UTR of the ERK2 gene in NSCLC cells. Fourthly, depletion of ERK1/2 reduced the migration and invasion of NSCLC cells. Combined depletion of ERK1/2 had a greater effect on cell migration than depletion of either one separately. Finally, the MEK1/2 inhibitor Trametinib decreased YAP protein level and transcriptional activity of the Hippo pathway in NSCLC cell lines. Our results suggest that ERK1/2 inhibition participates in reducing YAP protein level, which in turn down-regulates expression of the downstream genes of the Hippo pathway to suppress migration and invasion of NSCLC cells.

Background: The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance and its activation is aberrant in several types of cancer including mesothelioma. Protein kinase CK2 affects several cell signaling pathways through the mechanism of phosphorylation., Methods: Protein and mRNA levels of CK2α and Gli1 were tested by quantitative RT-PCR and immunohistochemistry staining in mesothelioma samples and cell lines. Down-regulated Gli1 expression and transcriptional activity were demonstrated by RT-PCR, Western blot and luciferase reporter assay., Results: In this study, we show that CK2α is over-expressed and a positive regulator of Hegdehog/Gli1 signaling in human malignant pleural mesothelioma. First of all, we found that the mRNA levels of CK2α and Gli1 were broadly elevated and correlated (n = 52, r = 0.401, P < 0.05), compared with LP9 (a normal mesothelial cell line). We then investigated their expression at the protein level, and found that all the 7 mesothelioma cell lines tested showed positive staining in CK2α and Gli1 immunohistochemistry. Correlation analysis by Pearson test for CK2α and Gli1 expression in the 75 mesothelioma tumors and the 7 mesothelioma cell lines showed that the two protein expression was significantly correlated (n = 82, r = 0.554, P < 0.01). Furthermore, we demonstrated that Gli1 expression and transcriptional activity were down-regulated after CK2α was silenced in two mesothelioma cell lines (H28 and H2052). CK2α siRNA also down-regulated the expression of Hh target genes in these cell lines. Moreover, treatment with a small-molecule CK2α inhibitor CX-4945 led to dose-dependent inhibition of Gli1 expression and transcriptional activity. Conversely, forced over-expression of CK2α resulted in an increase in Gli1 transcriptional activity in H28 cells., Conclusions: Thus, we report for the first time that over-expressed CK2α positively regulate Hh/Gli1 signaling in human mesothelioma.

Purpose: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare primary peritoneal malignancy. Its prognosis has been improved by an aggressive locoregional treatment combining extensive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prognostic factors are currently poorly defined for this disease but are essential if treatment is to be standardized., Methods: Twenty-eight patients with DMPM, who were considered preoperatively to be candidates for CRS and HIPEC between June 1998 and August 2010 at our institution, were selected for this study. Medical records and histopathological features were retrospectively reviewed and 24 clinical, histological, and immunohistochemical parameters were assessed for their association with overall survival by univariate and multivariate analyses., Results: The following factors were significantly associated with overall survival by univariate analysis: predominant histological growth pattern in the epithelioid areas, nuclear grooves in the epithelioid areas, atypical mitoses, and calretinin and GLUT1 expression by immunohistochemistry in the epithelioid areas. Expression of the facilitative glucose transporter protein GLUT1 in the epithelioid areas was the only factor independently associated with overall survival by multivariate analysis., Conclusions: GLUT1 expression appears to be an indicator of poor prognosis in DMPM. Standard histological classification of DMPM may not be adequate to select patients for aggressive locoregional treatments, such as CRS and HIPEC. Multicenter validation of the prognostic factors identified in this preliminary study is needed to refine patient selection for potential cure.

Objective: To study the relationship between expression of galectin-3 (Gal-3) and osteopontin (OPN) in occult metastasis in non-small cell lung cancer., Methods: Forty-six patients of non-small cell lung cancer (NSCLC) from January 2006 to October 2007 were selected. There were 28 males and 18 females, aged from 33 to 77 years old. The levels of lung tissues Gal-3 and OPN were detected by RT-PCR, and the levels of blood plasma's were measured by ELISA., Results: There were 12 patients who had metastasized. In un-metastasis group the Gal-3 and OPN mRNA expression levels were significantly lower than that in metastasis group: mean value were 0.07 +/- 0.17 and 0.17 +/- 0.25 in un-metastasis group, while 0.73 +/- 0.23 and 0.79 +/- 0.24 in metastasis group. Blood plasma levels of Gal-3 (18.8 +/- 7.9) microg/L and OPN (153.5 +/- 63.5) microg/L in NSCLC which were detected from metastasis group were higher than un-metastasis group of (9.2 +/- 5.6) microg/L and (89.2 +/- 24.0) microg/L., Conclusions: High serum levels of Gal-3 and OPN and high expression of Gal-3 and OPN mRNA in NSCLC are closely related to the occurrence and metastasis of NSCLC. They may be indexes of evaluating the occult metastasis in NSCLC.

Purpose: To investigate the prognostic value of systemic exposure to etoposide (Area Under the concentration Curve (AUC(VP16))) on overall survival (OS) in patients with small cell lung cancer (SCLC)., Patients and Methods: Data from 52 patients with limited stage (n=17) or metastatic (n=35) SCLC were analysed. They received at least two courses of etoposide (120mg/(m(2)day) on 3 days) combined with either doxorubicin-ifosfamide (AVI, n=29) or platinum compounds (carboplatin: n=16; cisplatin: n=7). Population pharmacokinetic-pharmacodynamic (PK-PD) study was performed using NON-linear Mixed Effect Model (NONMEM) and Splus software with univariate and multivariate analyses., Results: Etoposide plasma concentration vs. time was described by a two compartment model. Etoposide clearance (CL) was significantly dependant on serum creatinine (Scr). Ifosfamide (IFO) coadministration increased etoposide clearance by 28% (median CL(VP16): 2.42L/h vs. 1.89L/h, p<0.0005) leading to a reduced systemic exposure (median AUC(VP16): 260mgh/L vs. 339mgh/L). No influence of body surface area (BSA) on CL(VP16) was observed. Median percent decrease of absolute neutrophil count (ANC) after the first chemotherapy course was greater when etoposide 24h concentration was above 0.33mg/L (88% vs. 0%, p=0.028). Median OS was significantly longer in patients treated without ifosfamide (11.0 months vs. 7.0 months, p=0.049) and in patients with CL(VP16)<2.22L/h (14 months vs. 7 months, p=0.013) and AUC(VP16)>254.8mgh/L (11 months vs. 7 months, p=0.048). The independent prognostic factors regarding OS were LDH, CL(VP16) and AUC(VP16)., Conclusion: In this study it was found that CL(VP16) is reduced in patients with elevated serum creatinine, whilst ifosfamide coadministration increases CL(VP16) and reduces AUC(VP16), demonstrating the interaction between VP16 and ifosfamide. CL(VP16) and AUC(VP16) correlate significantly with overall survival of patients with SCLC patients receiving etoposide regimens.

Unlabelled: To investigate the K-ras gene mutations in asbestos and welding-fumes related human lung cancer (hLC), comparing with the mutational spectrum of K-ras gene in non-occupational hLC, 8 cases of non-occupational hLC, 9 cases of asbestos-related hLC and 4 cases of welding-fumes related hLC were collected. The techniques of genomic DNA extraction, nested-polymerase chain reaction (PCR), polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and DNA direct sequencing were employed., The Results: showed the mutation frequencies of K-ras gene were 25% in non-occupational hLC and welding-fumes related hLC, whereas 44.4% in asbestos-related hLC. Mutations mainly occurred in codons 12 and 15. A mutation of codon 13 was detected in welding-fumes related hLC. The type of base substitution was principally G-->T transversion in non-occupational hLC, whereas mainly G-->A transition in asbestos and welding-fumes related hLC. THE RESULTS suggested there were obvious differences of K-ras gene mutations among non-occupational hLC, asbestos and silica related hLC. Therefore, different mechanisms of carcinogenesis were implicated among them. However, no speific spectrum of K-ras gene mutation can be derived from welding-fumes related hLC because of the limitation of samples.

Crystalline silica was recently classified as a human carcinogen by the International Agency for Research on Cancer (IARC). However, the direct genotoxic effect of silica in humans remains unclear. We examined the p53 and K-ras gene mutations in lung cancer in workers with silicosis (LCWS). DNA was extracted from paraffin-embedded tissues and examined by PCR-RFLP, PCR-SSCP, and DNA sequencing. The mutation frequencies of p53 gene were high, but the mutation distributions in exons and among the histological types of LCWS differed from those of common (i.e., not silicosis-related) lung cancer. Furthermore, no mutations in codon 12 of K-ras gene (predominant in common lung cancer) were found in LCWS. These findings in the mutational spectrum support a carcinogenic effect of silica dust at the DNA molecular level.

The accumulation of mutant p53 protein in cancer cells was observed by immunohistochemistry analysis. DNA was extracted from paraffin-embedded tissue. Exons 5, 7 and 8 were amplified and studied by PCR-SSCP and sequencing analysis. Ten cases of asbestos associated cancer tissue were studied, of which five cases had adenocarcinoma, and the other five had mesothelioma, squamous carcinoma, small cell lung cancer, adenosquamous carcinoma and malignant lymphoma respectively. Employing monoclonal antibody PAb1801, five cases were found to be mutant p53 protein positive. Seven cases were found to have mutations by PCR-SSCP. A total of 7 cases (8 mutations) were found to be positive and 4 cases were found to be positive by both of these analyses. Of the 8 mutations found by SSCP analysis, 4(50%, 4/8) were clustered in exon 8. A high mutation frequency was noticed in adenocarcinoma (80%, 4/5). Sequencing analysis on two specimens revealed two hotspot mutations. In codon 234, TAC for tyrosin was mutated to AAC for asparagine by a T to A transversion of the first letter. In codon 273, CGT for arginine was mutated to AGT for serine by a C to A transversion of the first letter. In conclusion, the mutation of p53 gene is common in asbestos associated cancers. However, the mutational spectrum of asbestos associated cancers might be different from that of non-asbestos associated cancers.

The thoracic localization of endometriosis may involve the pulmonary pleura and the diaphragm, or the bronchopulmonary parenchyma, according to mechanisms which appear to be quite different. The principal clinical manifestations express themselves depending on their localization, a pneumothorax in the first case and hemoptysis in the second. One clinical characteristic, however, applies to them all, a rhythm strictly related to periods. The current methods of visualization of the pleura enable a macroscopic diagnosis to occur in the former cases in 64% and the body scanner now localizes the second in all cases. Treatment by Danatrol is often strikingly effective in a few months, notably in the cases with parenchymal localization.