Expression of l1 cell adhesion molecule and morphologic features at the invasive front of colorectal cancer

To obtain the correlation between morphologic features in the invasive fronts of colorectal cancer (CRC) and L1 cell adhesion molecule (L1CAM) expression, 275 CRCs were assessed with L1CAM immunostaining and 29 CRCs were examined for L1CAM messenger RNA (mRNA) expression. Based on immunostaining, the positive rate of L1CAM expression increased according to the grade of tumor budding (P = .0002) and solid cancer nests (SCNs; P = .0046). L1CAM mRNA levels at the invasive front of the tumor were higher than those at the center of the tumor (median, 3.7-fold). The gap of L1CAM mRNA level between the invasive front and the central area was 7.3-fold in tumors having SCN lesions, whereas it was 1.9-fold in tumors having non-SCN lesions (P = .0004). L1CAM expression was correlated with nodal involvement in protein and mRNA levels (P = .0007 and P = .036, respectively). Tumor regulation of L1CAM expression is associated with morphologic features at the invasive front in CRC.     

T-cell leukemia translocation-associated gene (TCTA) protein is required for human osteoclastogenesis

Synovial tissues of patients with rheumatoid arthritis (RA) include factors regulating bone resorption, such as receptor activator NF-κB ligand (RANKL), TNFα, IL-6, IL-17 and IFNγ. However, in addition to these cytokines, other factors expressed in synovial tissues may play a role in resorbing bone. Here, our objective was to identify novel proteins expressed in synovial tissues of RA that regulate human osteoclastogenesis. Proteins were purified from synovial tissues of patients with RA, using gel filtration chromatography, ion-exchange chromatography, reverse-aspect HPLC, and mass spectrometry. We evaluated the effects of the purified fractions on human osteoclastogenesis induced by RANKL and M-CSF. We determined the amino acid sequences showing inhibitory activity on human osteoclastogenesis. In addition, we synthesized novel peptides from the molecule including the amino acid sequences. Then, we evaluated the effects of the peptides and antibodies against the molecule on human osteoclastogenesis from monocytes and mature osteoclasts, and on pit formation by mature osteoclasts using Osteologic^R discs. We examined the effect of the peptide on the expression of both mRNA and protein of NFATc1. We also examined the effect of RANKL on the expression of mRNA of the molecule on osteoclasts and macrophages. We identified a small peptide including Gly-Gln-Asn (GQN) with inhibitory activity on human osteoclastogenesis. We then found that GQN is included in the amino acid sequence of the extra-cellular domain of TCTA protein, which is expressed ubiquitously in normal human tissues, but whose function has not been clarified. We designed novel peptides, including GQN, from the sequence of TCTA protein. One of these peptides (29-mer), but not a scrambled peptide for the 29-mer peptide, potently inhibited RANKL-induced human osteoclastogenesis. The peptide also inhibited pit formation of mature human osteoclasts and suppressed the formation of large osteoclasts in the culture of mature osteoclasts. Furthermore, polyclonal antibodies against TCTA protein suppressed the formation of large osteoclasts in the cultures of both monocytes and mature osteoclasts, supporting our hypothesis. Peptide A did not significantly inhibit the expression of both mRNA and protein of NFATc1 in osteoclasts. Our novel peptide and polyclonal antibodies against the peptide inhibited human osteoclastogenesis and the function of mature osteoclasts, preventing cellular fusion by TCTA protein and a putative counterpart molecule.     

Effects of oral care on development of oral mucositis and microorganisms in patients with esophageal cancer

We evaluated the effects of special oral care using a toothbrush with combined irrigation and suctioning functions, along with povidone-iodine to treat oral bacteria and mucositis, in esophageal cancer patients undergoing chemoradiotherapy. In the special care group, oral hygiene was performed 3 days a week after dinner. Bacteria in saliva and plague samples were measured at various sampling points after chemoradiotherapy. The incidence of mucositis was significantly reduced in the special care group in comparison with the control group. Total streptococci were significantly decreased in the opportunistic pathogens-positive and lower-level mutans streptococci control group during chemoradiotherapy, but they were not reduced in the opportunistic pathogens-negative and higher-level mutans streptococci control groups or in the special care group. Our results showed that a special oral care regimen enabled the total population of streptococci microflora to remain stable, was negatively correlated with opportunistic pathogens and positively correlated with mutans streptococci infection, and prevented the development of mucositis.     

Oxygen administration, cerebral blood flow velocity, and dynamic cerebral autoregulation

INTRODUCTION: Hyperoxia is reported to decrease steady-state cerebral blood flow (CBF). In addition, dynamic cerebral autoregulation would be altered. Hyperoxia may improve dynamic cerebral autoregulation, contrary to hypoxia. However, no previous studies have examined changes in steady-state CBF velocity (CBFV) and alterations of dynamic cerebral autoregulation during acute exposure to hyperoxia. We, therefore, evaluated dynamic cerebral autoregulation simultaneously with steady-state CBFV during stepwise hyperoxia under oxygen administration. METHODS: There were eight healthy volunteers who were examined under normoxic (21% O2) and hyperoxic conditions in stepwise fashion to 40%, 70%, and 100% O2. Mean blood pressure (MBP) in the radial artery was measured via tonometry, and CBFV in the middle cerebral artery was measured by transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis of beat-to-beat changes in MBP and CBFV. RESULTS: End-tidal CO2 decreased significantly at 70% and 100% O2. Steady-state CBFV decreased significantly at F1O2 > or = 40%, while MBP was unchanged. Associated with these changes, cerebral vascular resistance index increased at 70% and 100% O2. Transfer function gain and coherence remained unchanged at all levels of F1O2. DISCUSSION: These results suggest that hyperoxemia and hypocapnia reduce steady-state CBFV and increase cerebral vascular resistance during oxygen administration. This reduction in steady-state CBFV occurs even during mild hyperoxia < or = 40% O2 and becomes obvious at 70% O2 with hypocapnia. However, dynamic cerebral autoregulation may remain unchanged during hyperoxia, even with apparent changes in steady-state CBFV.     

CT Findings of Ruptured Intramural Hematoma of the Aorta Extending Along the Pulmonary Artery

Mediastinal hematoma extending along the pulmonary artery is a rare complication of Stanford type A classic (double-barreled) aortic dissection. Rupture from the posterior aspect of the aortic root penetrates the shared adventitia of the aorta and pulmonary artery. From this location, hematoma can spread along the adventitial planes of the pulmonary arteries out into the lungs. We report a case of ruptured intramural hematoma of the aorta (IMH) extending along the pulmonary artery. To our knowledge, this finding in patients with IMH has not been reported in the literature.     

A case of chronic myeloid leukemia occurring during treatment for chronic lymphocytic leukemia

Since the progression of chronic lymphocytic leukemia(CLL)is long and requires lengthy primary disease management, the risk of double primary cancers and secondary cancer due to treatment has become an issue in western countries with a high incidence of CLL. However, the coexistence with chronic myeloid leukemia(CML)is rare even in the West, and no cases have been reported in Japan. At this time, we would like to report a rare case of CML coexisting during the progression of CLL. The patient was a 68-year-old woman. As she had entered the advanced stage of B-cell chronic lymphocytic leukemia(B-CLL), fludarabine, a purine analog agent, was administered. Two years later, a high-granulocyte dominant white blood cell count began to appear. BCR/ABL analysis by FISH was 97. 6%positive, and the chromosomal test was t(9:22)(q34:q11), so CML was diagnosed. Coexistence of CML in CLL can mainly be classified into three types; CML preceding CLL, CLL preceding CML, and simultaneous occurrence, and the most common, as in this case, long progression CLL preceding CML. At this time, we performed a mainly bibliographical consideration according to the main occurrence type, including the possibility of secondary CML due to fludarabine.     

A case of metastatic colon cancer in which repetition of standard treatment proved effective

In palliative chemotherapy, a focus on palliative treatment is recommended in cases that are unresponsive to multiple drugs. Careful judgment is needed, however, because when treatment is inadequate, cases that are considered to be unresponsive may include some in which chemotherapy would be effective. We treated a patient with metastatic colon cancer who was judged to be unresponsive to multiple drugs at another hospital, yet repetition of standard therapy proved effective. We report this case as an instructive example of the importance of maintaining dose intensity. The patient was a 60-year-old man. Lung metastasis appeared after he had undergone proctectomy and received adjuvant chemotherapy by his previous doctor. Low-dose intensity IFL therapy, FOLFOX4 therapy (once a month), and FOLFIRI therapy (once only) had been performed, but the patient's condition worsened and he was referred to our hospital. This case could not be considered unresponsive to multiple drugs because the treatment had been insufficient, and so we restarted FOLFIRI treatment with the international standard dose and obtained control of the disease. Treatment was then continued, and the patient died 2 years and 11 months after he was first examined at our hospital. Simple palliative treatment alone should not be given unthinkingly when patients are referred for outpatient palliative care. Full consideration of the dosing and schedule is needed.     

A novel automated method for measuring the effect of analgesics on formalin-evoked licking behavior in rats

The behavioral assessment of pain is essential for the analysis of pain mechanisms and the evaluation of analgesic drugs. The formalin test is one of such methods widely used as a model of injury-induced pain in rodents. This test is manually demanding and the recording of results is left to the subjectivity of the experimenters. Thus we developed a novel automated method to estimate the pharmacological response in formalin-induced licking behavior in rats using a multicolor detection technique. Two color markers were preliminarily applied to rats-yellow dye on the mouth and fluorescent green tape on the right hind paw. Behaviors of the animals were recorded from both above and below the subject, by a dual-view digital video camera system. After injection with formalin into the hind paw, rats exhibited a biphasic display of licking behavior. Licking time was measured by the sum of frames where the distance between these markers was less than an appropriate threshold of distance (TD). The split-plot analysis of variance demonstrated that the sum of squares of differences in licking time between manual and automated measurement was minimized when TD = 20mm. In addition, frames in which moving velocity of these markers is less than 2.5mm/s was neglected for calculation in order to eliminate sedative effect on the recorded data. On these conditions, subcutaneous administration of morphine in rats dose-dependently decreased formalin-elicited nociceptive responses. These results suggest that under optimal conditions the automated technique when applied to pharmacological studies are more reliable and efficient than if they are manually recorded.     

Port-site metastasis after retroperitoneoscopy-assisted nephroureterectomy and cystectomy for bladder cancer invading the ureter: a case report

We report a case of port-site metastasis of bladder cancer after left retroperitoneoscopy-assisted nephroureterectomy and cystectomy. The patient was a 73-year-old man with a chief complaint of gross hematuria. The diagnosis was invasive bladder cancer with bone metastasis. He received two courses of chemotherapy (methotrexate, vinblastine, adriamycin, cisplatin), and this resulted in resolution of the bone metastases. Two months later, abdominal and pelvic computed tomography showed a bladder tumor invading the left lower ureter with hydronephrosis. Left retroperitoneoscopy-assisted nephroureterectomy and cystectomy were performed. The patient was unable to undergo systemic chemotherapy because of renal dysfunction. Four months later, a lateral abdominal wall tumor was found at a port-site, and needle biopsy confirmed this to be metastatic urothelial carcinoma. Clinicians need to be aware of port-site metastasis, particularly in patients with UC, and take steps to prevent it during laparoscopic procedures.     

Stereochemistry of pladienolide B

Pladienolide B is a 12-membered macrolide isolated from Streptomyces platensis Mer-11107. It showed potent in vitro and in vivo antitumor activities and is a potential lead for novel antitumor agents. The absolute configurations at ten chiral centers were determined on the basis of spectral data of pladienolide B and its chemical transformation products.