Cytotoxic effect of essential oil of thyme (Thymus broussonettii) on the IGR-OV1 tumor cells resistant to chemotherapy

The anti-tumor effect of the Moroccan endemic thyme (Thymus broussonettii) essential oil (EOT) was investigated in vitro using the human ovarian adenocarcinoma IGR-OV1 parental cell line OV1/P and its chemoresistant counterparts OV1/adriamycin (OV1/ADR), OV1/vincristine (OV1/VCR), and OV1/cisplatin (OV1/CDDP). All of these cell lines elicited various degrees of sensitivity to the cytotoxic effect of EOT. The IC50 values (mean ± SEM, v/v) were 0.40 ± 0.02, 0.39 ± 0.02, 0.94 ± 0.05, and 0.65 ± 0.03 percent for OV1/P, OV1/ADR, OV1/VCR, and OV1/CDDP, respectively. Using the DBA-2/P815 (H2d) mouse model, tumors were developed by subcutaneous grafting of tumor fragments of similar size obtained from P815 (murin mastocytoma cell line) injected in donor mouse. Interestingly, intra-tumoral injection of EOT significantly reduced solid tumor development. Indeed, by the 30th day of repeated EOT treatment, the tumor volumes of the animals were 2.00 ± 0.27, 1.35 ± 0.20, and 0.85 ± 0.18 cm³ after injection with 10, 30, or 50 æL per 72 h (six times), respectively, as opposed to 3.88 ± 0.50 cm³ for the control animals. This tumoricidal effect was associated with a marked decrease of mouse mortality. In fact, in these groups of mice, the recorded mortality by the 30th day of treatment was 30 ± 4, 18 ± 4, and 8 ± 3 percent, respectively, while the control animals showed 75 ± 10 percent of mortality. These data indicate that the EOT which contains carvacrol as the major component has an important in vitro cytotoxic activity against tumor cells resistant to chemotherapy as well as a significant antitumor effect in mice. However, our data do not distinguish between carvacrol and the other components of EOT as the active factor.

Cytotoxic effect of essential oil of thyme (Thymus broussonettii) on the IGR-OV1 tumor cells resistant to chemotherapy.

The anti-tumor effect of the Moroccan endemic thyme (Thymus broussonettii) essential oil (EOT) was investigated in vitro using the human ovarian adenocarcinoma IGR-OV1 parental cell line OV1/P and its chemoresistant counterparts OV1/adriamycin (OV1/ADR), OV1/vincristine (OV1/VCR), and OV1/cisplatin (OV1/CDDP). All of these cell lines elicited various degrees of sensitivity to the cytotoxic effect of EOT. The IC50 values (mean +/- SEM, v/v) were 0.40 +/- 0.02, 0.39 +/- 0.02, 0.94 +/- 0.05, and 0.65 +/- 0.03% for OV1/P, OV1/ADR, OV1/VCR, and OV1/CDDP, respectively. Using the DBA-2/P815 (H2d) mouse model, tumors were developed by subcutaneous grafting of tumor fragments of similar size obtained from P815 (murin mastocytoma cell line) injected in donor mouse. Interestingly, intra-tumoral injection of EOT significantly reduced solid tumor development. Indeed, by the 30th day of repeated EOT treatment, the tumor volumes of the animals were 2.00 +/- 0.27, 1.35 +/- 0.20, and 0.85 +/- 0.18 cm(3) after injection with 10, 30, or 50 microL per 72 h (six times), respectively, as opposed to 3.88 +/- 0.50 cm(3) for the control animals. This tumoricidal effect was associated with a marked decrease of mouse mortality. In fact, in these groups of mice, the recorded mortality by the 30th day of treatment was 30 +/- 4, 18 +/- 4, and 8 +/- 3%, respectively, while the control animals showed 75 +/- 10% of mortality. These data indicate that the EOT which contains carvacrol as the major component has an important in vitro cytotoxic activity against tumor cells resistant to chemotherapy as well as a significant antitumor effect in mice. However, our data do not distinguish between carvacrol and the other components of EOT as the active factor.

Ets transcription factors bind and transactivate the core promoter of the von Willebrand factor gene.

von Willebrand factor (vWF) gene expression is restricted to endothelial cells and megakaryocytes. Previous results demonstrated that basal transcription of the human vWF gene is mediated through a promoter located between base pairs -89 and +19 (cap site: +1) which is functional in endothelial and non endothelial cells. Two DNA repeats TTTCCTTT correlating with inverted consensus binding sites for the Ets family of transcription factors are present in the -56/-36 sequence. In order to analyse whether these DNA elements are involved in transcription, human umbilical vein endothelial cells (HUVEC), bovine calf pulmonary endothelial cell line (CPAE), HeLa and COS cells were transfected with constructs containing deletions of the -89/+19 fragment, linked to the chloramphenicol acetyl transferase (CAT) reporter gene. The -60/+19 region exhibits significant promoter activity in HUVEC and CPAE cells only. The -42/+19 fragment is not active. Mutations of the -60/+19 promoter fragment in the 5' (-56/-49) Ets binding site abolish transcription in endothelial cells whereas mutations in the 3' (-43/-36) site does not. The -60/-33 fragment forms three complexes with proteins from HUVEC nuclear extracts in electrophoretic mobility shift assay which are dependent on the presence of the 5' Ets binding site. Binding of recombinant Ets-1 protein to the -60/-33 fragment gives a complex which also depends on the 5' site. The -60/+19 vWF gene core promoter is transactivated in HeLa cells by cotransfecting with Ets-1 or Erg (Ets-related gene) expression plasmids. In contrast to the wild type construct, transcription of the 5' site mutants is not increased by these expressed proteins. The results indicate that the promoter activity of the -60/+19 region of the vWF gene depends on transcription factors of the Ets family of which several members like Ets-1, Ets-2 and Erg are expressed in endothelium. Cotransfection of Ets-1 and Erg expression plasmids is sufficient to induce the -60/+19 vWF promoter activity in HeLa cells.

Comparison of the 5'-flanking sequences of the human and bovine von Willebrand factor-encoding genes reveals alternation of highly homologous domains with species-specific Alu-type repeats.

von Willebrand factor (vWF), a multimeric glycoprotein important for hemostasis, is specifically synthesized in endothelial cells and in platelet precursors (megakaryocytes). Recent studies from two laboratories, including ours, were published regarding the cell-specific transcription of reporter genes controlled by the human (hu) vWF promoter in transfected bovine (bo) endothelial cells and cells of non-endothelial origins. In order to verify that the regulatory domains previously characterized in the 5' region of hu vWF are also present in bo vWF, we have sequenced 1.9 kb upstream from the cap site, plus five exons. The comparison of human and bovine exons two to five shows homology of 83% at the nucleotide (nt) level and 78% at the deduced amino-acid sequence level. The bovine and human exons one, which are non-coding and span 233 and 250 bp, respectively, are only 64% homologous. In the first exon, potentially involved in endothelial-cell-specific transcription, the binding site for factor Sp1 is present in bo vWF, whereas the GATA sequence is replaced by a GACA sequence. The sequence corresponding to the human basal promoter, located between nt -89 and +19, is well conserved with 82% homology. However, the human TAATTA sequence (at nt -32) considered to be a TATA box, is replaced by TCATTA, and the CCAAT element at nt -18 is replaced by CCTGT. Among domains involved in transcription, the negative regulatory domain located 5' from the core promoter is highly conserved. The bovine sequence upstream from the first intron can be aligned with the human sequence up to nt -656 which is located in a polymorphic poly(GT)18-26 sequence. At this site, the bovine DNA contains an insertion of 523 bp which corresponds to a bovine Alu-type art2 repeat of 331 bp flanked by bovine microsatellites. The art2 sequence is an Alu-type repeat in artiodactyls with at least 100,000 copies in the bovine genome. Upstream from this insertion, 368 bp of the bovine sequence can be aligned with the human counterpart up to a 9-bp element which flanks an human Alu repeat which is absent from the bovine DNA. Upstream of the human Alu insertion and a duplicate of the 9-bp element, the two sequences are again homologous.

Hepatic abscess due to occult biliary stones.

The advent of radiologic percutaneous drainage of abdominal abscesses has revealed that a significant percentage involve a fistulous communication to other organs or structures. We present two cases in which abscessograms revealed unsuspected fistulous communication to an incompletely or intermittently obstructed biliary tree with retained stones.

Non-Hodgkin's lymphoma presenting as periampullary mass with obstructive jaundice.

A case of periampullary lymphoma presenting as obstructive jaundice is described. A description of the radiographic findings and differential diagnosis is provided.

Demonstration of pleural tube track tubularity.

The inflammatory reaction that is caused by the placement of a tube in the pleural space persists after tube removal and may be observed on chest roentgenograms. One radiological presentation of this reaction is a lucent stripe, which represents localized iatrogenic pneumothorax in the track of the tube. The possibility that this stripe may represent a tubular track is not generally appreciated. We report two instances in which the three-dimensional tubular nature of the tracks is demonstrated. Failure to correlate such a stripe with roentgenograms showing the previous placement of the chest tube at the site of a track may lead to confusion and potentially serious misinterpretation.

Dilated pulmonary venous confluence presenting as a mass in mitral stenosis.

Pulmonary varices are rare venous anomalies which typically present as masses. Since they are usually clinically insignificant, varices must be diagnostically distinguished from parenchymal tumors and mediastinal adenopathy so one may adhere to a conservative medical approach. This report reviews the literature and illustrates a convergence of varices that presented as a larger sized mass than previously described by others.