Tumor cell invasion from the marginal sinus into extranodal veins during early-stage lymph node metastasis can be a starting point for hematogenous metastasis

Aim: To investigate whether tumor cells in a lymph node (LN) can invade from the marginal sinus into extranodal veins via vessel branches that communicate with intranodal veins and whether this can be a starting point for hematogenous metastasis at the early stage of LN metastasis.Methods: Vascular and lymphatic networks of LNs in MXH10/Mo-lpr/lpr mice were investigated using three-dimensional micro-computed tomography and histological methods. Flow in the blood vessel networks of LNs was investigated by fluorescence microscopy. Tumor cells were injected into the subiliac LNs of MXH10/Mo-lpr/lpr mice to induce metastasis to the proper axillary LNs. Tumor development in the proper axillary LN was detected using an in vivo bioluminescence imaging system. A two-dimensional image of the proper axillary LN microvasculature was reconstructed using a contrast-enhanced high-frequency ultrasound system.Results: Extranodal veins communicated with intranodal veins via branches that penetrated the capsule, and blood flowed from intranodal veins to extranodal veins. Tumor cells that had metastasized to the marginal sinus invaded these communicating veins to develop hematogenous metastases.Conclusion: Metastatic LNs that would be considered by clinical imaging to be stage N0 can be a starting point for hematogenous metastasis. The study findings highlight the need for the development of novel techniques for the diagnosis and treatment of early-stage LN metastasis, i.e., when standard diagnostic imaging might incorrectly classify the LN as stage N0

Metastatic Ureteral Involvement of Non-Small Cell Lung Cancer

Metastases from a variety of malignant tumors can involve the ureters, but ureteral involvement by lung cancer is extremely rare and usually described at autopsy. We report a rare case of a 76-year-old man who presented with a three-month history of right flank dullness and was noted to have a nonhomogeneous retroperitoneal mass with hydronephrosis of the right kidney on computed tomography of the abdomen. Computed tomography of the thorax showed a nodule in the lower lobe, measuring 3 × 2 cm, in the right lung. After excluding the presence of other primary tumors and metastases, we reached a final diagnosis of solitary retroperitoneal metastasis of adenocarcinoma of the lung. Although rare, in patients of non-small cell lung cancer, presence of hydronephrosis should alert the physician to the possibility of metastasis

Mechanistic studies on DNA damage by minor groove binding copper–phenanthroline conjugates

Copper–phenanthroline complexes oxidatively damage and cleave nucleic acids. Copper bis-phenanthroline and copper complexes of mono- and bis-phenanthroline conjugates are used as research tools for studying nucleic acid structure and binding interactions. The mechanism of DNA oxidation and cleavage by these complexes was examined using two copper–phenanthroline conjugates of the sequence-specific binding molecule, distamycin. The complexes contained either one or two phenanthroline units that were bonded to the DNA-binding domain through a linker via the 3-position of the copper ligand. A duplex containing independently generated 2-deoxyribonolactone facilitated kinetic analysis of DNA cleavage. Oxidation rate constants were highly dependent upon the ligand environment but rate constants describing elimination of the alkali-labile 2-deoxyribonolactone intermediate were not. Rate constants describing DNA cleavage induced by each molecule were 11–54 times larger than the respective oxidation rate constants. The experiments indicate that DNA cleavage resulting from β-elimination of 2-deoxyribonolactone by copper–phenanthroline complexes is a general mechanism utilized by this family of molecules. In addition, the experiments confirm that DNA damage mediated by mono- and bis-phenanthroline copper complexes proceeds through distinct species, albeit with similar outcomes

Standard and limitation of intraoperative monitoring of the visual evoked potential

Visual evoked potential (VEP) has been installed as one of the intraoperative visual function monitoring. It remains unclear, however, whether intraoperative VEP monitoring facilitates as a real time visual function monitoring with satisfactory effectiveness and sensitivity. To evaluate this, relationships between VEP waveform changes and postoperative visual function were analysed retrospectively. Intraoperative VEP monitoring was carried out for 106 sides (eyes) in 53 surgeries, including two intraorbital, 36 parasellar and 15 cortical lesions in Shinshu University Hospital under total intravenous anaesthesia. Red light flash stimulation was provided to each eye independently. VEP recording and postoperative visual function were analysed. In 103 out of 106 sides (97%), steady VEP monitoring was recorded. Stable VEP was acquired from eyes having corrected visual acuity greater than 0.4. VEP was not recorded in one side with corrected visual acuity of 0.3 and two sides in whom sevoflurane was used incidentally for anaesthesia. Transient VEP decrease was observed in three sides, but visual function was preserved. Permanent VEP decrease was seen in seven sides, which presented visual impairment postoperatively. In one side, visual acuity improved but minor visual field defect was encountered postoperatively, though VEP unchanged throughout the surgery. Intraoperative monitoring of VEP predicts postoperative visual function: reversible change in VEP means visual function to be preserved. Visual field defect without decrease in the visual acuity may not be predicted by VEP monitoring. Intraoperative VEP monitoring will be mandatory for surgeries harbouring a risk of visual impairment.ArticleACTA NEUROCHIRURGICA. 152(4):643-648 (2010)journal articl

Quantitative analysis of thrombopoietin receptors on human megakaryocytes

AbstractThrombopoietin (TPO), or c-MPL ligand, is the primary regulator of megakaryocyte and platelet production. TPO receptors expressed on human megakaryocytes derived from peripheral blood (PB) and cord blood (CB) progenitors cultured in the presence of TPO have now been analyzed quantitatively. Like those on human PB platelets, TPO receptors on the cultured megakaryocytes exhibited a molecular mass of approximately 80 kDa. Various characteristics of PB- and CB-derived megakaryocytes indicated that the former were more mature than the latter. Both PB- and CB-derived megakaryocytes expressed a single class of high-affinity TPO receptors, with 1933±772 (n=3) and 184±48 (n=4) sites per cell, respectively. These data indicate that the number of TPO receptors on human megakaryocytes increases with cell maturation