Pleuropulmonary blastoma. A rare childhood malignancy

Pleuropulmonary blastoma PPB is an extremely rare, intrathoracic neoplasm of early childhood with unfavorable outcome. We present a case of a 4-year-old boy with progressive dyspnea due to tension pneumothorax. After chest tube insertion, the CT scan showed large multilocular cystic lesions containing air and solid areas involving the right lower lobe, and its related pleura. Thoracotomy was carried out, and the cyst was removed with the pleural solid areas. Histopathological examination confirmed the diagnosis of PPB type II. Postoperatively, the patient was scheduled to start chemotherapy in a specialized pediatric oncology center to complete the treatment.     

Internalization of carcinogenic lead chromate particles by cultured normal human lung epithelial cells: formation of intracellular lead-inclusion bodies and induction of apoptosis

Occupational exposure to certain particulate hexavalent chromium [Cr(VI)] compounds, such as lead chromate, has been associated with lung cancer and respiratory tract toxicity. We have previously shown that apoptosis is a major mode of death in cultured rodent cells treated with soluble sodium chromate and particulate lead chromate. Here we report the cellular and molecular effects of lead chromate and sodium chromate in normal human lung small airway epithelial (HSAE) cells, which may be one of the targets for Cr(VI)-induced lung cancer and respiratory tract toxicity. Phagocytosed lead chromate particles and intracellular lead-inclusion bodies (LIB) were observed by transmission electron microscopy and confirmed by X-ray analysis. HSAE cells exposed to lead chromate and sodium chromate underwent dose-dependent apoptosis. The cellular uptake and genomic interactions of both Cr and lead (Pb) were examined by inductively coupled plasma mass spectrometry (ICPMS) coupled with a novel, direct-injection high-efficiency nebulizer (DIHEN). Using this approach, we have quantitated a dose-dependent formation of Cr-DNA adducts and DNA-associated Pb in lead chromate-treated HSAE cells. The formation of LIB in normal human lung cells exposed to lead chromate indicates that ionic Pb is released from the particles and thus might contribute to the cell toxicity caused by lead chromate. Internalization and dissolution of lead chromate particles and the interaction of ionic Cr and Pb with DNA, may be components of the mechanism of lead chromate carcinogenesis. Lead chromate-induced apoptosis may be a mechanism to eliminate cells with chromium- and/or lead-damaged DNA.     

Cytotoxic activity of the titanium alkoxide (OPy)2Ti(4AP)2 against cancer colony forming cells

A novel family of titanium alkoxides with two stable pyridinemethoxide moieties bound to a titanium metal center were synthesized and tested for cytotoxic activity on a variety of cancer cell lines using colony formation assays. One compound, (OPy)₂Ti(4AP)₂, where OPy is NC₅H₅CH₂O⁻, and 4AP is 4-aminophenoxide (⁻OC₆H₅(NH₂)-4), demonstrated increased cytotoxicity in breast, colon, and pancreatic cancer cell lines at 100 nanomolar levels with only short exposures. Further, (OPy)₂Ti(4AP)₂ had activity in colon and pancreatic cancer cell lines that are usually resistant to chemotherapy. This demonstrates that these titanium compounds may have a role in anti-cancer therapy, similar to platinum-based compounds, and the (OPy)₂Ti(4AP)₂ compound specifically deserves further investigation as an anti-cancer agent in chemo-resistant solid tumors.     

Hemin-dependent modulation of the lipid A structure of Porphyromonas gingivalis lipopolysaccharide

Porphyromonas gingivalis is a periopathogen strongly associated with the development of adult-type periodontitis. Both the virulence characteristics of periopathogens and host-related factors are believed to contribute to periodontitis. P. gingivalis lipopolysaccharide (LPS) displays a significant amount of lipid A structural heterogeneity, containing both penta- and tetra-acylated lipid A structures. However, little is known concerning how the lipid A structural content of P. gingivalis is regulated. Alterations in the lipid A content may facilitate the ability of P. gingivalis to modulate the innate host response to this bacterium. In this report, it is shown that the concentration of hemin in the growth medium significantly modulates the lipopolysaccharide lipid A structural content of P. gingivalis. Hemin is a key microenvironmental component of gingival cervicular fluid which is believed to vary depending upon the state of vascular ulceration. At low hemin concentrations, one major penta-acylated lipid A structure was found, whereas at high concentrations of hemin, multiple tetra- and penta-acylated lipid A structures were observed. Hemin concentrations, not iron acquisition, were responsible for the alterations in the lipid A structural content. The modifications of the lipid A structural content were independent of the LPS extraction procedure and occurred in a variety of laboratory strains as well as a freshly obtained clinical isolate. The known hemin binding proteins Kgp and HmuR contributed to the lipid A modulation sensing mechanism. To the best of our knowledge, this is the first report that hemin, a clinically relevant microenvironmental component for P. gingivalis, can modulate the lipid A structure found in a bacterium. Since tetra- and penta-acylated P. gingivalis lipid A structures have opposing effects on Toll-like receptor 4 activation, the alteration of the lipid A structural content may have significant effects on the host response to this bacterium.