Genome-wide survey of mRNA half-lives in Bacillus subtilis identifies extremely stable mRNAs.

We have used DNA microarrays to survey rates of mRNA decay on a genomic scale in early stationary-phase cultures of Bacillus subtilis. The decay rates for mRNAs corresponding to about 1500 genes could be estimated. About 80% of these mRNAs had a half-life of less than 7 min. More than 30 mRNAs, including both mono- and polycistronic transcripts, were found to be extremely stable, i.e. to have a half-life of > or =15 min. Only two such transcripts were known previously in B. subtilis. The results provide the first overview of mRNA decay rates in a gram-positive bacterium and help to identify polycistronic operons. We could find no obvious correlation between the stability of an mRNA and the function of the encoded protein. We have also not found any general features in the 5' regions of mRNAs that distinguish stable from unstable transcripts. The identified set of extremely stable mRNAs may be useful in the construction of stable recombinant genes for the overproduction of biomolecules in Bacillus species.

A Swedish study of chemoradiation in squamous cell carcinoma of the esophagus.

This multicenter study describes the development of a chemoradiation protocol for the treatment of non-metastatic squamous cell carcinoma of the esophagus. Eighty patients were treated with three courses of chemotherapy (cisplatinum and 5-fluorouracil) with concomitant radiotherapy (40 Gy) during the last two courses of chemotherapy. Esophagectomy was performed, when feasible. If no operation was performed, patients were planned to receive a target dose of 64 Gy. Toxicity was mainly attributable to hematological impairment and led to two adjustments of the treatment protocol (addition of filgrastim and lowering of the 5-fluorouracil dose). These changes made it possible to administer the planned treatment in a gradually higher proportion of patients (13/23 [57%] before changes of treatment compared with 30/36 [83%] after changes). Treatment-related mortality was 3.75% (3 patients, associated with leucopenic septicemia after chemotherapy). Fifty-four patients were resected. No per- or postoperative mortality was encountered. The complete response (pathological CR) rate in operated patients was 46% (27/59 patients) after chemoradiation. In the whole series the CR rate (including clinical CR for non-resected patients) was 44%. With a minimum follow-up of 37 months, the 3-year survival for the whole group was 31% compared with 57% for the CR patients. Total 5-year survival thus far (July 1999) is 26%.

Chest wall sarcoma: outcome in 22 patients after resection requiring thoracic cage reconstruction.

Purpose. To evaluate the outcome after resection of malignant chest wall sarcoma, requiring reconstruction of the chest wall.Subjects. Twenty-two patients, 15 with primary tumours, were operated on in our institution between 1983 and 1996. Four patients underwent surgery after a previous intralesional or marginal excision and three patients because of a local recurrence.Methods. The tumour was resected 'en bloc', including skin, muscle and thoracic skeleton. When necessary, adjacent organs invaded by the tumour, such as lung, pericardium and diaphragm, were also removed to obtain a wide margin. Reconstruction of the chest wall was performed with Marlex mesh (n=9), methylmethacrylate cement (n=2) or a Marlex methylmethacrylate 'sandwich' (n=11).Results. The median tumour size was 9.5 (2-20) cm. The most common type of tumour was chondrosarcoma (12 cases). No patient died in hospital. Five patients required reoperation because of complications, two patients because of loosening of the acrylate prosthesis, two because of necrosis of soft tissue coverage and one was reoperated because of bleeding. Four patients died of generalized tumour disease between 5 and 77 months after surgery and one patient died of a local recurrence 32 months after the primary operation. Seventeen patients are alive, with a median follow-up of 36 (4-162) months. Microscopic radicality (negative margin) was achieved in 17 patients but 5 of these had local recurrences. Two of five patients with positive margins had a local recurrence of the tumour. Of the seven patients with local recurrences, two also developed metastases.Discussion. Large chest wall sarcomas can be successfully resected and the chest wall reconstructed with low morbidity and mortality.

Release of atrial natriuretic peptide during pulmonary artery clamping in man.

The vasodilating hormone atrial natriuretic peptide (ANP) is secreted from the heart in response to atrial wall stretch, but knowledge of the time course of ANP secretion after acute releasing stimuli is limited. The time from stimulus to release of immunoreactive atrial natriuretic peptide (irANP) was investigated by unilaterally clamping the pulmonary artery in 12 patients undergoing pulmonary surgery. The second messenger to ANP-induced vascular relaxation, plasma cyclic guanosine monophosphate (p-cGMP), was measured as an indirect marker of the vascular effects of ANP. Immediately after applied clamping, p-irANP (baseline level 15.4 +/- 2.9 pmol l-1) started to increase, reaching a significant, although moderate, increase (11 +/- 4%, P < 0.05) after 2 min. This elevation of p-irANP remained during the entire clamping period (+13 +/- 6%, P < 0.05 vs. baseline). Within 1 min of declamping, p-irANP returned to the baseline level. No conclusive alterations in p-cGMP were observed. The prompt ANP response to the applied stimulus, and the return to baseline after declamping, may indicate the presence of a short time-acting releasing mechanism of ANP.

Cytogenetic analysis of short-term cultured squamous cell carcinomas of the lung.

Cytogenetic analysis of 122 primary squamous cell carcinomas of the lung revealed clonal abnormalities in 56 tumors. Karyotypes with simple numerical changes were found in 32 tumors: 45,X,-Y in 28, 47,XY,+7/45,X-Y, in two, 47,XY,+Y/45,X,-Y and 47,XY,+20/45,X,-Y in one tumor each. A super-numerary ring chromosome was the sole anomaly in two tumors. Complex structural changes were found in 22 tumors. The chromosomes most frequently involved in structural rearrangements were chromosomes 1 (15 tumors), 3, 7, and 11 (10 tumors each), 5 and 6 (nine tumors each), and 2, 8, and 12 (eight tumors each). The bands and regions most often affected were 1p11-13 and 5cen (six tumors each), 11p11, 14p11-13, 15cen, and 17p11-12 (five tumors each), and 12p13 and 13cen (four tumors each). The only recurrent changes were the whole-arm rearrangements i(5)(p10) (five tumors) and i(6)(p10), der(9;15)(q10;q10), and der(13;15)(q10;q10) (two tumors each). The most prominent genomic imbalances were, apart from losses of the Y chromosome, losses from 1p, 3p, 5q, 6q, 8p, 13p, and 14p and gains from 1q and 5p.

Karyotypic characterization of bronchial large cell carcinomas.

Cytogenetic analysis of short-term cultures from 26 primary bronchial large cell carcinomas and 1 metastasis from a primary large cell carcinoma revealed clonal chromosome abnormalities in 20 tumors and a normal karyotype in 6. No outgrowth was obtained in 1 case. Simple aberrations were present in 3 tumors; in 1, the only change was a reciprocal translocation between chromosomes 1 and 6, in another the sole anomaly was a supernumerary marker ring chromosome and in a third loss of the Y chromosome was the only clonal change. The remaining 17 tumors had complex karyotypes. The chromosomes most frequently involved in structural rearrangements were chromosomes 1, 2, 3, 5, 6, 7, 8, 10, 11, 13, 14 and 17. The bands most frequently affected were 1q11-12, 1p13, 7q11, and 17p11-13. The rearrangements led to repeated losses of 1p, 1q, 3p, 6q, 7q and 17p and gains of 5q and 7p. The emerging karyotypic picture of large cell lung carcinomas indicates more similarities with adenocarcinomas than with other pathologic subgroups of lung cancer.

Acute and delayed effects of radiotherapy in patients with oesophageal squamous cell carcinoma treated with chemotherapy, surgery and pre- and postoperative radiotherapy.

Among 73 patients with oesophageal squamous cell carcinoma treated with chemotherapy (cisplatin + 5-fluorouracil), surgery and pre- and postoperative radiotherapy, the 1-year survival rate was 68% and the 5-year rate 26%. The treatment was well tolerated, though there were 11 cases of pericardial or pleural effusion, in all of which the effusion was benign and could be successfully treated with pleural aspiration and/or pleurodesis, pericardiocentesis, or in one case pericardectomy.

Karyotypic abnormalities in adenocarcinomas of the lung.

Cytogenetic analysis of 114 adenocarcinomas of the lung revealed clonal abnormalities in 67 tumors. The chromosome numbers ranged from near-diploid to hypertetraploid. Clonal abnormalities seen as the sole anomaly were loss of the Y chromosome (21 tumors), trisomy 7 (2 tumors), and trisomy 12 (1 tumor). A supernumerary ring chromosome was the only clonal change in 4 tumors. The bands most often affected were 17p11-13 (13 cases), 1q10-12 and 1p22 (10 cases each), 1p11-13 and 1q21 (9 cases each), and 11p11, 11p15 and 15p11-13 (6 cases each). The chromosomes most frequently involved in structural rearrangements were chromosomes 1 (30 cases), 11 (20 cases), 3 (17 cases), 17 and 7 (16 cases each). Repeated loss of material from chromosome arms 1p, 3p, 6q, 11p, and 17p and gains of 1q were found. Recurrent structural changes were del(1)(p22) and i(5)(p10) (5 cases each) i(1)(q10), i(13)(q10), i(14)(q10) and del(17)(p11) (3 cases each). We found no abnormalities that seemed to be specifically associated with pulmonary adenocarcinomas, but isochromosomes i(1)(q10), i(5)(p10) and i(13)(q10) and changes of 6q were present in our series at frequencies higher than those generally seen in the other main types of lung cancer.

Recombinations of chromosomal bands 6p21 and 14q24 characterise pulmonary hamartomas.

Cytogenetic analysis of short-term cultures from seven pulmonary hamartomas revealed an abnormal karyotype in six of them. The most characteristic aberration was an exchange of material between 6p21 and 14q24, found in three tumours. Abnormalities of either 6p or 14q were seen in another two hamartomas. Other regions that were rearranged more than once were 12q (three times) and 17p (twice), sometimes in exchange with 6p or 14q and giving rise to complex derivative chromosomes. Only one tumour had aberrations that did not involve 6p, 12q, 14q, or 17p. These results-together with the data on three previously reported pulmonary hamartomas, two of which also had t(6;14)-show that recombinations between 6p21 and 14q24 are common, and hence probably pathogenetically important. The data support the view that these tumours are genuine neoplasms rather than developmental anomalies. The coexistence of a common 14q24 breakpoint in uterine leiomyomas and pulmonary hamartomas indicates that a gene important in the genesis of both tumours exists in this band.

Malignant esophageal strictures: treatment with a self-expanding nitinol stent.

A self-expanding esophageal nitinol stent was implanted under fluoroscopic guidance in 40 patients with malignant esophageal strictures and clinically significant dysphagia. The strictures were caused by squamous cell carcinoma (n = 14), adenocarcinoma (n = 12), recurrent anastomotic carcinoma (n = 8), and mediastinal tumors (n = 6). Eight stents were balloon dilated to maximum diameter immediately after insertion. Sixteen stents self-expanded to maximum diameter within 24 hours, and the other stents expanded to maximum diameter during further observation. There were no serious stent-related complications, and the dysphagia was reduced considerably in all patients immediately after stent insertion. Persistent tumor bleeding occurred in two patients, and ingrowth of tumor into the stent was seen in eight patients. Two stents occluded due to tumor ingrowth but were successfully recanalized with endoscopic laser coagulation. At the end of the study, 28 patients were dead with a mean survival of 2.9 months (range, 0.1-7.0 months), and 12 patients were alive with a mean follow-up of 8.8 months (range, 4.0-15.0 months).

Cytogenetic analysis of six bronchial carcinoids.

Short-term cultures from four typical and two atypical primary bronchial carcinoids were cytogenetically analyzed. A lung metastasis from one of the atypical carcinoids was also analyzed. Of the four typical carcinoids, two had normal chromosome complements, while the other two had the karyotypes 46,X, -X, +7/47,XX, +7/47,XX, +X/46,XX and 47,XX, +7/46,XX. Both atypical carcinoids had chromosome abnormalities. One had the karyotype 45-46,X, -X,del(1)(q32),add(17)(p13), +add(19)(p13), -22, +r/47,XX, +X. The second carcinoid had the karyotype 78-81,XXY, +Y, +1,t(2;8)(q21;q24), +3, +4, +del(4) (q25), +5, +6,der(6)t(6;6)(q21;p21)x2, +7, +7, -10,add(14)(p11-13), +19, -21, +1-4mar. The metastasis from this carcinoid had the same aberrations, except that the del(4)(q25) had been lost and one to two markers had been gained.

Pseudodiploid karyotypes in adenosquamous carcinomas of the lung.

Pseudodiploid karyotypes with clonal structural rearrangements were observed in short-term cultures from two adenosquamous carcinomas (ASC) of the lung, a tumor type hitherto virtually uncharacterized cytogenetically. The karyotypes were 46,XX,der(1)t(1;14)(q44;q22),add(9)(q34) in the first tumor and 46,XX,i(17)(q10) in the second tumor. We suggest that ASC of the lung differ from other lung cancers by having pseudodiploid instead of massively aneuploid tumor stemlines.

Effect of chemotherapy and radiotherapy on squamous cell carcinoma of the esophagus. A preoperative radiologic evaluation.

In a series of 82 patients with epidermoid carcinoma of the esophagus, 68 were available for review of barium examinations and 44 for review of CT examinations showing the effect of preoperative treatment. After 3 courses of chemotherapy--Cisplatinum and 5-fluorouracil, and 24 Gy of presurgical irradiation--over a total of 10.5 weeks, the patients were ready for surgery. The results of the presurgical radiographic examinations were compared with the findings of histopathologic studies after surgery. Where both the CT and the barium examination showed a complete response, none of the patients had remaining macroscopic cancer. When healing with stenosis was included, CT and barium studies in combination were necessary to exclude a residual macroscopic tumor. Therefore, a combination of barium esophagography and CT is recommended to estimate the preoperative effect of treatment.

Cisplatin and 5-FU combined with radiotherapy and surgery in the treatment of squamous cell carcinoma of the esophagus. Palliative effects and tumor response.

The combination of cisplatin (90-120 mg/m2) and 5-fluorouracil (5-FU) (1,000 mg/m2/day in continuous infusion for five days) was given for 2-3 cycles, prior to combined radiotherapy and surgery, to 73 patients with esophageal squamous cell carcinoma, 60 with limited disease (LD), and 13 with extensive disease (ED) (i.e. with metastasis) of whom 3 had recurrent disease. Before preoperative radiotherapy among 60 LD patients, 12 (20%) had complete response, 21 (35%) partial response, 25 (42%) had stable disease, and 2 (3%) progressive disease. Swallowing was improved in 35/73 (48%) of the cases. In the resected specimens, no tumor was found in 8/53 (15%) of the cases, microscopic tumor in 18/53 (34%) and macroscopic tumor in 27/53 (51%). In the ED group, complete response of distant metastases was obtained in 6/13 (48%) of the patients, one of whom is still alive with no evidence of disease 62 months after the start of treatment.

Rearrangement of 9p13 as the primary chromosomal aberration in adenoid cystic carcinoma of the respiratory tract.

Two adenoid cystic carcinomas, one of the nasal cavity, the other a bronchial tumor, were cytogenetically analyzed. The former had a t(6;9)(q21-22;p 13-21) as the sole karyotypic abnormality. The latter had two related abnormal clones, resulting in the mosaic karyotype 46,XY,t(9;17)(p13;p13)/46,Y,t(X;6)(p22;q23),t(9;17)(p13;p13). The karyotypic profiles of the two cases, the only respiratory tract adenoid cystic carcinomas that have been cytogenetically characterized, differ little from those of previously reported adenoid cystic carcinomas of the major salivary glands, underscoring the fundamental biologic similarity among these tumors even when they develop from different structures and in different anatomical sites and organs. Because in the second case the t(9;17) obviously must have preceded the t(X;6), we conclude that both tumors had rearrangement of 9p13 as the primary cytogenetic change. The data thus add to the evidence that 6q changes are frequent, albeit at least sometimes secondary, aberrations in malignant salivary gland tumors. A subset of adenoid cystic carcinomas instead have rearrangement of 9p as the primary, and presumably pathogenetically essential, abnormality.

Evaluation of the palliative effect of radiotherapy for esophageal carcinoma.

149 patients with carcinoma of the esophagus treated with radiotherapy were evaluated. Eighty-one patients had treatment with palliative intent and 68 with curative intent. The 4-year actuarial survival was 1 and 5% respectively. The tumor size, Karnofsky index (KI) and radiation dose were prognostic factors. The duration of palliation of the patients dysphagia was dose-dependent.