Background Watering eyes is a common late adverse event associated with S-1 chemotherapy; however, the frequency and predictive factors are not known. Methods This study included 304 consecutive gastric cancer patients treated with adjuvant S-1 monotherapy for 1 year at Shizuoka Cancer Center. We retrospectively evaluated the frequency of watering eyes, and explored other nonhematological adverse events during the first course of S-1 monotherapy which could become predictive factors for watering eyes. Results The severest grade of watering eyes during S-1 monotherapy was grade 2 in 41 patients (13.5 %) and grade 3 in 36 patients (11.8 %). The median time to onset of grade 2 and grade 3 watering eyes was 82 days (range 6-344 days) and 249 days (range 84-653 days), respectively, and the median cumulative S-1 dose at the onset of grade 2 and grade 3 watering eyes was 4174 mg/m 2 (range 491-16,095 mg/m 2 ) and 10,243 mg/m 2 (range 4943-16,341 mg/m 2 ), respectively. Multivariate analysis showed that anorexia (odds ratio 2.37, P = 0.008), oral mucositis (odds ratio 3.86, P = 0.0003), skin hyperpigmentation (odds ratio 3.84, P = 0.0001), and rash (odds ratio 3.76, P = 0.01) observed during the first course were significantly associated with watering eyes. Conclusion The risk of watering eyes was higher in patients who also had anorexia, oral mucositis, skin hyperpigmentation, or rash during first course of S-1 monotherapy than in those without them.
A 30-year-old man, who had been treated with craniospinal irradiation, total-body irradiation, and bone marrow transplantation for acute lymphoblastic leukemia at 20 years of age, complained of dysphagia. The patient had spike fever with leukocytosis (19,020/μl). Serum granulocyte colony-stimulating factor (G-CSF) level was also increased (53.7 pg/ml). Immunohistochemistry revealed positive staining for anti-G-CSF antibody in carcinoma cells obtained by endoscopic biopsy. The patient was diagnosed with G-CSF-producing locally advanced esophageal squamous cell carcinoma. The clinical diagnosis was T4; tumor invaded aorta, with regional lymph node metastases (N1). The patient underwent transthoracic esophagectomy with three-field lymph node dissection and gastric tube reconstruction following a radiation dose of 41.4 Gy with 5-fluorouracil continuous infusion as neoadjuvant therapy. There were no viable cancer cells in the resected esophageal specimen and lymph nodes. The patient had no evidence for typical risk factors for developing esophageal cancer. After the operation, neutrophils and G-CSF decreased to normal levels. The patient had recurrence of regional and distant multiple lymph node metastases at 3 months after operation.
e14623 Background: TIVAPS are widely used for cancer chemotherapy. Bevacizumab, a key drug for mCRC, associates with AEs such as thromboembolism, bleeding, and impaired wound healing. Bevacizumab may complicit in increasing incidence of TIVAPS related AEs. To assess the incidence of TIVAPS related AEs in mCRC patients who received chemotherapy with and without bevacizumab. Methods: We retrospectively reviewed the medical records of consecutive patients whose TIVAPS were placed at our institution between Apr. 2004 and Apr. 2009. Major selection criteria were histologically proven colorectal adenocarcinoma, metastatic disease, and receiving chemotherapy after TIVAPS placement. We assessed the incidence of AEs occurred from the first administration of chemotherapy via TIVAPS to TIVAPS removal, death, or the last follow-up. We compared the incidence of TIVAPS related AEs in the cases bevacizumab was administered (group A) with that in the cases without bevacizumab administration (group B). Results: TIVAPS was placed 549 times for 505 patients, and 544 TIVAPS placements for 501 patients were analyzed. Bevacizumb was administered in 174 patients (32%), and median duration of bevacizumab therapy was 9.2 months. Characteristics of the cases in the group A and B were: male (60% and 59%); primary site colon (60% and 57%); catheterized in left subclavian vein (85% and 81%); history of prior chemotherapy (53% and 60%); median time from TIVAPS placement to administration of chemotherapy (1 day and 1 day). Incidence of common AEs in the group A and B were: infection (7.5% and 6.8%); venous thromboembolism (3.4% and 1.4%); TIVAPS occlusion (2.3% and 1.9%); delay of wound healing (1.1% and 0.5%); hematoma (0.6% vs 0%). Median time to AE in the group A and B was 21 months and 9 months. There was no significant difference in the incidence of TIVAPS related AEs between group A and B. During median observation period of 40.5 months, no arterial thrombotic event or AE resulted in death occurred. Conclusions: Addition of bevacizumab did not increase TIVAPS related AEs during chemotherapy for mCRC.
Question: A wide range of CFTR expressing epithelia are permanently in motion and thus exposed to different mechanical forces. There is evidence that distension of the pulmonary epithelium activates a Cl-secretion (Bogdan et al. 2008, Pflugers Arch) and that the activity of CFTR could be influenced by mechanical forces (Zhang et al. 2010, Nat Cell Biol). The underlying mechanisms of this activation are currently unknown. The aim of this study was to investigate the impact of mechanical forces on CFTR activity in native pulmonary epithelia. Methods: Freshly dissected Xenopus laevis lungs were mounted in modified Ussing-chambers that allowed the application of hydrostatic pressure (HP, 5 cm or 10 cm fluid-column) while changes of short-circuit current (I SC) were recorded. HP was applied in the absence and presence of the CFTR inhibitor (GlyH-101) and a CFTR activator (IBMX) to determine whether or not CFTR activity is influenced by HP-induced strain. Results: Apical application of HP (5 cm) led to a decrease of net ion current (11±2%). In presence of GlyH-101 the HP-induced current decrease was significantly augmented (5 cm: 28±4%; p<0.01; 10 cm: 44±6%; p<0.01). IBMX a known secretagogue increased ISC, although there was no change of the HP effect (10 cm) in comparison with controls (HP effect without IBMX; p=0.08). Conclusions: HP activates a Cl-secretion in native lung ep-ithelium that is sensitive to CFTR inhibitors but not affected by secretagogues. These data indicate that CFTR activity is regulated by membrane strain and that CFTR is a mechano-sensitive channel. Question: The tyrosine kinase Janus kinase-3 (JAK3) fosters proliferation and counteracts apoptosis of lymphocytes and tumor cells. The gain of function mutant A572VJAK3 was discovered in acute megakaryoplastic leukemia. JAK3 is inactivated by replacement of lysine by alanine in the catalytic subunit (K855AJAK3). Regulation of cell proliferation and apoptosis involves Cl-channels. The present study thus explored the effect of JAK3 on the small conductance Cl-channel ClC-2. Methods: ClC-2 was expressed in Xenopus oocytes with or without wild type JAK3, A568VJAK3 or inactive K851A-JAK3 and the Cl-channel activity determined by dual electrode voltage clamp. Channel protein abundance in the cell membrane was determined utilizing chemiluminescence. Results: Expression of ClC-2 was followed by a marked increase of cell membrane conductance. The conductance of ClC-2 expressing oocytes was significantly decreased following coexpression of JAK3 or A568VJAK3, but not by coexpression of K851AJAK3. Exposure of the oocytes expressing ClC-2 together with A568VJAK3 to the JAK3 inhibitor WHI-P154 (22 μM) increased the conductance. Coexpression of A568VJAK3 decreased the ClC-2 protein abundance in the cell membrane of ClC-2 expressing oo-cytes. The decline of conductance in ClC-2 and A568VJAK3 coexpressing oocytes following inhibition of channel protein insertion by brefeldin A (5 µM) was similar in oocytes expressing ClC-2 with A568VJAK3 and oocytes expressing ClC-...
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