Growth characteristics and metastatic potential of seven intestinal carcinoma lines serially passaged in syngeneic rats

Summary Transplantable tumour lines were obtained from one duodenal carcinoma induced byN-methyl-N-nitro-N-nitrosoguanidine in the Lewis rat and from six colonic carcinomas induced by 1,2 dimethylhydrazine in BDIX or Fisher rats. The tumours were serially transplanted by the subcutaneous route into homologous syngeneic rats. The seven tumours differ from one another in their histological structure, five of them being well or moderately differentiated adenocarcinomas, and in their capacity to produce neutral or acidic mucins. The seven tumours also differ in their growth rate. The seven lines produced metastases; the metastatic potential and the location of the metastases differed from one line to another. The seven lines kept their original differentiation characteristics through multiple passages, representing several years of transplantation into syngeneic hosts. These tumours represent a useful and diversified model of metastatic intestinal carcinoma, available for basic research and therapeutic trials.     

Key enzymes for the degradation of benzoate,m- and p-hydroxybenzoate by some members of the order Actinomycetales

A preliminary screening of numerous species of the order Actinomycetales, especially of the genera Mycobacterium, Nocardia, Rhodococcus, Pseudonocardia, and Streptomyces, showed that many of them are able to metabolize benzoate (B) and p-hydroxybenzoate (pHB) as indicated by growth and change of color of the pH-indicator of an agar medium. Subsequent experiments with liquid cultures which allowed the analysis of substrate utilization by thin layer chromatography confirmed these results. The study of the degradative pathway proved that B was metabolized via catechol (C), pHB via protocatechuate (P) and m-hydroxybenzoate (mHB) via gentisate (G). The aromatic ring of C and P was subjected to an ortho-cleavage; only one strain of Noc. asteroides degraded C via a meta-cleavage, but P via an ortho-cleavage. Cell free extracts of four selected organisms exhibited activity of C-1,2-dioxygenase (C-1,2-O) and/or P-3,4-dioxygenase (P-3,4-O), depending on the growth substrate used for precultivation. In Streptomyces C-1,2-O was only found in cells grown on B, and P-3,4-O only in cells grown on pHB. On the contrary, in Rhodococcus rhodochrous B-cells oxidized C as well as P, while P-cells possessed only P-3,4-O-activity.     

Computed tomography diagnosis of tracheobronchopathia osteochondroplastica

Tracheobronchopathia osteochondroplastica (TO) is a rare benign disease characterized by the presence of osseous and cartilaginous submucosal nodules projecting into the tracheobronchial tree. Most cases are asymptomatic and discovered incidentally at post‐mortem. We identified a case of TO on thoracic spiral CT and confirmed the diagnosis on bronchoscopy. This article reviews the imaging characteristics of TO, and shows the 3‐D virtual bronchoscopic and multiplanar reconstruction appearances of TO.     

Antagonists of growth hormone releasing hormone and bombesin inhibit the expression of EGF/HER receptor family in H-69 small cell lung carcinoma

Effects of in vivo treatment with antagonists of growth hormone-releasing hormone (GHRH), JV-1-65 and MZ-J-7-110, and bombesin/gastrin-releasing peptide antagonist RC-3940-II, on the EGF receptor (EGFR) family, were investigated in H-69 SCLC. Tumors were analyzed by RT-PCR, immunoblotting and binding assays. Treatment with these analogs reduced the binding capacity of EGFR by 18-64%, and inhibited the mRNA expression for EGFR, HER-2 and -3 by 27-75.4, 17-26.3, and 13.8-46.6%, respectively. The antagonists also decreased the protein levels for EGFR by 21-34%, HER-2 by 36-68% and HER-3 by 43-49%. This is the first demonstration that antiproliferative effects of GHRH antagonists are associated with a downregulation of EGF/HER receptors.     

Alterations of EGFR/HER, angiogenesis and apoptosis pathways after therapy with antagonists of growth hormone releasing hormone and bombesin in non-small cell lung cancer

New therapeutic strategies are necessary to improve the treatment of lung cancer. We investigated the effects of bombesin/gastrin-releasing peptide (GRP) antagonist, RC-3940-II, and growth hormone-releasing hormone (GHRH) antagonists, MZ-J-7-114 and MZ-J-7-118, on the expression of epidermal growth factor receptor (EGFR)/HER (-2, -3, and -4) family, angiogenic factors, VEGF-A and VEGF receptors (VEGF-R1 and VEGF-R2), and the apoptotic molecules Bax and Bcl-2, in H-460 and A-549 non-small cell lung carcinomas (NSCLC). Nude mice bearing xenografts of H-460 and A-549 NSCLC were treated daily with these peptide analogues for 4 weeks. The treatment resulted in growth inhibition of H-460 by 22-77% and A-549 NSCLCs by 64-84%. The inhibition of tumor growth was associated with a down-regulation of members of EGFR/HER family. A significant reduction of the levels of expression of EGFR/HER family on both tumors varied from 29-96%: the greatest inhibition being induced by RC-3940-II. Similarly, a significant decrease in the levels of VEGF-A in tumors by 19-60% and VEGF receptors (VEGF-R1, 24-74% and VEGF-R2, 25-50%) was detected after therapy. An up-regulation of Bax by 21-63% and a down-regulation of Bcl-2 by 23-39% was observed only for H-460 NSCLC. Our study demonstrates that human H-460 and A-549 NSCLC, express receptors for GHRH and bombesin/GRP, and respond to the respective antagonists. The antagonists of bombesin/GRP and GHRH could provide a new strategy for treatment of NSCLC through down-regulation of EGFR/HER family and an interference with the angiogenic and apoptotic pathways.     

The role of thyroid FNA cytology in pediatric malignant lesions: An overview of the literature

When one is dealing with pediatric thyroid lesions, fine‐needle aspiration is the first diagnostic tool for the correct characterization of these nodules. Despite the apparent infrequency of thyroid cancers in children, recent data from the National Cancer Institute prove that the incidence has been increasing, especially in adolescents. With the same data, a higher prevalence of well‐differentiated cancers can be estimated, with 90% diagnosed as papillary thyroid cancer. Nonetheless, some publications have demonstrated that some specific malignant variants are more frequent in children and have a more aggressive behavior that justifies the increased number of surgical procedures. For this reason, the American Thyroid Association recommends the performance of neck ultrasonography and fine‐needle aspiration cytology (FNAC) for the evaluation of pediatric thyroid nodules. Accordingly, as reported in adult thyroid series, several authors have documented the high sensitivity and diagnostic accuracy of FNAC in pediatric series; they have also shared the same problematic issues encountered in adult populations, mostly in the diagnosis of indeterminate lesions. To provide precise clinical and/or surgical management, the correct cytological identification of specific malignant histotypes/entities should be mandatory because lymph nodes, distant metastases, and extrathyroidal infiltration are more frequent within specific histotypes. A perusal of the literature shows that their identification has not been extensively studied and investigated in cytological samples. This review focuses on the analysis of data from the literature on the evaluation of malignancies and specific morphological features in pediatric thyroid lesions. Cancer Cytopathol 2017;125:594‐603 . © 2017 American Cancer Society.     

Proteomics-based identification of α1-antitrypsin and haptoglobin precursors as novel serum markers in infiltrating ductal breast carcinomas

Background

The identification of pathological markers of breast cancer for either diagnosis, treatment response or for survival is of critical importance.

Methods

Serum protein profiling using 2-DE separations coupled to matrix-assisted laser desorption ionization mass spectrometry has been used to explore protein alterations in patients with infiltrating ductal breast carcinomas (IDCA). Sera from 39 breast cancer patients and 40 healthy controls were selected for screening study using 2-DE combined with MS. The protein expression patterns obtained after the depletion of high abundance proteins was determined by coomassie blue G-250 stain after 2-DE electrophoresis.

Results

Six proteins that expressed differentially in the IDCA group were found. The expression levels of four isoforms corresponding to haptoglobin precursor and two isoforms of α1-antitrypsin precursor (α1-AT) were upregulated in sera from breast cancer patients. There was an increased expression of both proteins in the sera of patients with various tumor stages (I, II, III) in comparison to healthy women. Applying immunohistochemistry, we further validated α1-AT immunoreactivity in 51 formalin-fixed paraffin-embedded sections of breast tumors. Enhanced expression of α1-AT like activity has been found in IDCA breast tumors, as well as, in different histological types of breast cancer. No significant association has been found with lymph node occurrence, while in high tumor categories a tendency to an increased expression of α1-AT has been found, thereby suggesting a possible role of this protein in tumor growth.

Conclusions

These proteins may constitute new and useful markers of breast cancer that offer a clue to a better understanding of inflammatory pathways and carcinogenesis events linked to breast cancer progression.