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Wolfgang Hohenforst-Schmidt,1 Paul Zarogoulidis,2,3 Kaid Darwiche,3 Thomas Vogl,4 Eugene P Goldberg,5 Haidong Huang,6 Michael Simoff,7 Qiang Li,6 Robert Browning,8 J Francis Turner,9 Patrick Le Pivert,10 Dionysios Spyratos,2 Konstantinos Zarogoulidis,2 Seyhan I Celikoglu,11 Firuz Celikoglu,11 Johannes Brachmann11II Medical Clinic, Coburg Hospital, University of Wuerzburg, Coburg, Germany; 2Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany; 4Department of Diagnostic and Interventional Radiology, Goethe University of Frankfurt, Frankfurt, Germany; 5Biomaterials Science and Engineering, Department of Materials Science and Engineering, University of Florida, FL, USA; 6Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People's Republic of China; 7Bronchoscopy and Interventional Pulmonology, Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University, School of Medicine, MI, USA; 8Pulmonary and Critical Care Medicine, Interventional Pulmonology, National Naval Medical Center, Walter Reed Army Medical Center, Bethesda, USA; 9Pulmonary Medicine, University of Nevada School of Medicine, National Supercomputing Center for Energy and the Environment University of Nevada, Las Vegas, USA; 10Interventional Drug Delivery Systems and Strategies (ID2S2), Medical Cryogenics, Jupiter, FL, USA; 11Pulmonary Department, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, TurkeyAbstract: Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa–IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%–1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin–based systemic chemotherapy in (higher) standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of life than a non-small cell lung cancer in ECOG 0 of the same tumor node metastasis [TNM]-stage without central obstruction) for a chemotherapy-only protocol that differs from conventional cisplatin-based doublet chemotherapy by the route, target site, and dose paves the way for broader applications of this technique. Finally, future perspectives of this treatment and pharmaceutical design for intratumoral administration are presented.Keywords: cisplatin, lymph nodes, chemotherapy, intratumoral, lung cancer

Revealing the lung tumor genome has directed the current treatment strategies toward targeted therapy. First line treatments targeting the genome of lung tumor cells have been approved and are on the market. However, they are limited by the small number of patients with the current investigated genetic mutations. Novel treatment administration modalities have been also investigated in an effort to increase the local drug deposition and disease control. In the current study, we investigated the safety of the new nonviral vector 2-diethylaminoethyl-dextran methyl methacrylate copolymer (DDMC; Ryujyu Science), which belongs to the 2-diethylaminoethyl-dextran family by aerosol administration. Thirty male BALBC mice, 2 month old, were included and divided into three groups. However, pathological findings indicated severe emphysema within three aerosol sessions. In addition, the CytoViva technique was applied for the first time to display the nonviral particles within the pulmonary tissue and emphysema lesions, and a spectral library of the nonviral vector was also established. Although our results in BALBC mice prevented us from further investigation of the DDMC nonviral vector as a vehicle for gene therapy, further investigation in animals with larger airways is warranted to properly evaluate the safety of the vector.

Midbrain tegmental lesions, which prevent the hindlimb extensor (HLE) component of maximal electroshock seizures (MES), were found to have no effect on the electroshock, flurothyl, or pentylenetetrazol (PTZ) seizures thresholds. However, these lesions were found to antagonize the HLE component of the maximal PTZ seizure, and to elevate the threshold for electroshock induced tonic flexion. These findings suggest that lesion of the midbrain tegmentum involving the superior cerebellar peduncle and/or the midbrain reticular formation antagonize the tonic component of generalized seizures, but have little or no effect on the clonic component.

A bilaterally induced mechanical lesion of the midbrain was highly effective in abolishing the hindlimb extensor (HLE) component of the maximal electroshock seizures (MES) in rats. Although these lesions produced damage to a variety of midbrain structures, correlations between different lesion placements and effects in the MES test provided evidence that damage to superior cerebellar peduncle (PCS) and/or reticular formation (RF) was responsible for inhibition of hindlimb extension. Moreover, discretely placed electrolytic lesions disrupting either the PCS or the RF were found to abolish the hindlimb extensor component of the MES test. These findings are consistent with the work of other investigators showing that total cerebellectomy abolishes the HLE component of MES and suggest that activity in the cerebellum and the midbrain reticular formation plays a major role in regulating the tonic phase of electroshock induced seizures.

Fox, Alfred E. (Warner-Lambert Research Institute, Morris Plains, N.J.), George L. Evans, Frank J. Turner, Benjamin S. Schwartz, and Ansel Blaustein. Stimulation of nonspecific resistance to infection by a crude cell wall preparation from Myocobacterium phlei. J. Bacteriol. 92:1-5. 1966.-Exposure of large quantities of viable Mycobacterium phlei to attrition in a colloid mill resulted in 90 to 95% disruption of the organisms. Isolation of the crude cell wall preparation was accomplished by centrifugation of the broken cells at 10,000 x g, resuspension of the sediment, and repeated centrifugation at 1,000 x g to remove intact cells. Single oral or parenteral doses of the cell wall preparation increased the resistance of mice and guinea pigs to experimental infection with Salmonella enteritidis, and of mice to Staphylococcus aureus, for prolonged periods after administration. Histological examination of the organs of mice treated orally or intraperitoneally revealed a lymphoid hyperplasia of the spleen and a Kupffer cell proliferation of the liver. The preparation was nontoxic to mice by the oral route at doses up to 5,000 mg/kg, and the intraperitoneal ld(50) was approximately 680 mg/kg.

This note examines critically recent attempts to identify or closely correlate lunar surface samples-on the basis of alpha-scattering analysis-with terrestrial igneous rocks (basalts) or with eucrite meteorites. Basalts show considerable variety; but all have chemical characteristics inherited from terrestrial mantle rock melted under a limited range of terrestrial pressure-temperature conditions. What is characteristic is not so much the content of any particular element or oxide-e.g., SiO(2) 47-52 per cent-but rather a complete chemical pattern in which such ratios as Fe/Mg and Ca/(Na + K) show consistent relationships to Si content. These are the chemical criteria that might be useful in comparing terrestrial basalt with extraterrestrial rocks. Basalts also have distinctive mineralogical and textural characteristics; and if a lunar or meteoritic rock is to be identified as basalt it must possess these, too.Turkevich's analysis of alpha-scattering data for lunar samples (Surveyor V) show significant departure from basaltic composition: Very high (Ca + K)/Na associated with distinctly high Fe/Mg. In basalts relatively high (Ca + K)/Na-in no case approaching the reported lunar values-tends to be associated with Fe/Mg values lower than average. The same "lunar" pattern of high (Ca + K)/Na and Fe/Mg appears in recorded analyses of eucrite meteorites. In the lunar samples, Ti is notably higher than in basalts, and even more so than in eucrites. If eucrites are of lunar origin their Ti values are, so far, a real anomaly.