Parallel administration of nanoliposomal irinotecan and levo-leucovorin for pancreatic cancer.

BACKGROUND: Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/levo-leucovorin (Levo-LV) was approved for unresectable pancreatic cancer (UR-PC) in March 2020 in Japan. Levo-LV is administered by intravenous infusion over 120 min following 90 min intravenous infusion of nal-IRI (conventional method), causing a significant burden on both patients and the outpatient chemotherapy room owing to the prolonged administration time. Thus, from July 2021, we introduced the simultaneous intravenous administration of nal-IRI and Levo-LV (parallel method) with the approval of the institutional regimen committee. METHODS: We retrospectively reviewed the data of 69 patients with UR-PC who received nal-IRI plus 5-FU/Levo-LV at our hospital between June 2020 and October 2021. We examined the safety of the parallel method and compared the treatment outcomes and administration times between the two methods. RESULTS: The median age was 66 years (54%, male). Disease statuses were locally advanced, metastatic, and postoperative recurrence after pancreatectomy in 7, 50, and 12 patients, respectively. Nal-IRI plus 5-FU/Levo-LV treatment was second and third-line or later in 35 and 34 patients, respectively. No intravenous line problems were observed during the parallel administration of nal-IRI and Levo-LV. Although there were no significant differences in response rates and adverse events between the two methods, the administration time was significantly shorter in the parallel method than in the conventional method. CONCLUSION: The parallel administration of nal-IRI and Levo-LV is clinically safe and not inferior in efficacy. Moreover, parallel administration may offer convenience to patients and healthcare workers by reducing administration time.

Impact of prior bevacizumab therapy on the incidence of ramucirumab-induced proteinuria in colorectal cancer: a multi-institutional cohort study.

BACKGROUND: The association between prior bevacizumab (BEV) therapy and ramucirumab (RAM)-induced proteinuria is not known. We aimed to investigate this association in patients with metastatic colorectal cancer (mCRC). METHODS: mCRC patients who received folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus RAM were divided into with and without prior BEV treatment groups. The cumulative incidence of grade 2-3 proteinuria and rate of RAM discontinuation within 6 months (6M) after RAM initiation were compared between the two groups. RESULTS: We evaluated 245 patients. In the Fine-Gray subdistribution hazard model including prior BEV, age, sex, comorbidities, eGFR, proteinuria ≥ 2 + at baseline, and later line of RAM, prior BEV treatment contributed to proteinuria onset (P < 0.01). A shorter interval between final BEV and initial RAM increased the proteinuria risk; the adjusted odds ratios (95% confidence intervals) for the intervals of < 28 days, 28-55 days, and > 55 days (referring to prior BEV absence) were 2.60 (1.23-5.51), 1.51 (1.01-2.27), and 1.04 (0.76-1.44), respectively. The rate of RAM discontinuation for ≤ 6M due to anti-VEGF toxicities was significantly higher in the prior BEV treatment group compared with that in the no prior BEV treatment group (18% vs. 6%, P = 0.02). Second-line RAM discontinuation for ≤ 6M without progression resulted in shorter overall survival of 132 patients with prior BEV treatment (P < 0.01). CONCLUSION: Sequential FOLFIRI plus RAM after BEV failure, especially within 55 days, may exacerbate proteinuria. Its escalated anti-VEGF toxicity may negatively impact the overall survival.

Efficacy and safety of mycophenolate mofetil in treating immune-related hepatitis induced by immune checkpoint inhibitor use: A retrospective study.

Background and Aim: To investigate the outcomes in eight Japanese patients with cancer treated with mycophenolate mofetil (MMF) and corticosteroids for immune checkpoint inhibitor treatment-induced severe immune-related hepatitis (ir-hepatitis) and the efficacy and safety of MMF. Methods: We retrospectively examined patient background, treatment course, as well as examination and imaging data using electronic medical records. Results: The ratio of male to female patients was 7:1, and the median age was 60 years (27-72 years). There were five and two cases of kidney cancer and malignant melanoma, respectively, and one case of lung cancer. The median number of days until MMF administration in addition to systemic corticosteroid therapy after the onset of ir-hepatitis was 14.5 (2-42). The patients were categorized as four "good responders" who showed an improvement in the liver function tests following MMF treatment and four "poor responders" who did not. Furthermore, the time from the onset of ir-hepatitis to initial MMF administration was significantly shorter in good responders (median 3 days, range 2-15 days) than in poor responders (median 25.5 days, range 14-42 days) (P = 0.042). No significant intergroup difference was observed in other clinical factors. No serious adverse events caused by MMF were observed in any case. Conclusions: According to these findings, early recognition of corticosteroid refractoriness and the use of MMF may be beneficial in patients with ir-hepatitis.

Efficacy and safety of Infliximab for steroid-resistant immune-related adverse events: A retrospective study.

The present study investigated outcomes of infliximab (IFX) treatment among 8 Japanese patients with various types of cancer (4 with malignant melanoma, 3 with lung cancer and 1 with renal cancer) who developed severe steroid-resistant immune-related adverse events (irAEs) in association with immune checkpoint inhibitors (ICIs) to determine its efficacy and safety. Information, including patient background, treatment progress, examination data and imaging data, was collected retrospectively from electronic medical records. Adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Specific ICIs used were anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibody preparations in 7, 2 and 5 patients, respectively. Specific irAEs included grade 3 diarrhea/colitis in 7 patients and disseminated intravascular coagulation and myocarditis attributed to autoimmune activation in 1 patient. The median duration between systemic steroid and IFX treatments was 9 (range, 2-39) days. A total of 3 patients responded to IFX, 1 of whom responded after one dose and 2 responded after two doses. Respective diseases improved to grade 0 after a median of 18 (range, 9-32) days. No AEs were attributable to IFX. Additionally, anti-cytomegalovirus (CMV) and antibacterial agents were administered in parallel given the presence of CMV and Clostridium difficile (CD) infections in all patients, except in 1 exhibiting a marked IFX response after one dose. The combination of highly immunosuppressive IFX and high-dose systemic steroid administration over a long period presumably predisposed the patients to opportunistic enteric infections. Accordingly, early initiation of IFX treatment in conjunction with systemic steroid therapy should be considered for severe diarrhea/colitis and other irAEs. However, the possibility for CMV and CD infections should be recognized, and for these the treatment strategy may need to be modified at an early stage.

[Effect of Relative Dose Intensity(RDI)-Guided Dose Adjustments of Palbociclib on Duration of Treatment in Patients with Severe Neutropenia].

The study subjects consisted of 54 patients with inoperable or recurrent breast cancer who were administered a combination of palbociclib plus endocrine therapy. We examined the onset of neutropenia during the first course of treatment and evaluated the influence that various risk factors had on treatment continuity. Patients with neutropenia Grade≥3 had significantly lower relative dose intensity(RDI) values during the first course of treatment than did patients with neutropenia Grade ≤2. Patients with neutropenia Grade≥3 showed significantly longer treatment to failure than did patients with neutropenia Grade≤2. These results suggest that the degree of neutropenia during the first course of treatment might contribute to treatment continuity and that it is important to improve the curative effect by maintaining appropriate RDI and by continuously administering palbociclib in patients with neutropenia Grade≥3.

Clinical and ex vivo laboratory comparison of the self-sealing properties and dimensional stability between the femtosecond laser and manual clear corneal incisions.

PURPOSE: To compare the self-sealing features and dimensional stability between the femtosecond laser (FL) and manual knife corneal incision. METHODS: For the clinical study, 29 consecutive eyes from 29 patients and 28 eyes from 28 patients who underwent cataract surgery with FL corneal incision and manual knife incision, respectively, were enrolled. Immediately after cataract surgery, the self-sealing features of the corneal incisions were evaluated. Scanning electron microscopy (SEM) images were obtained. For the experimental study, clear corneal incisions with a knife or FL with different energy settings (3, 6 and 9 µJ) were created in fresh porcine eyes, followed by a stress test. The incision width was measured before and after the stress test. RESULTS: In the clinical study, the knife group had a higher self-sealing score (0.60 ± 0.49 points) than the FL group (0.17 ± 0.38 points). In the experimental study, the deformation rate in the knife incision (5.04 ± 1.93) was significantly lower than that in the FL with any energy. The deformation rate in the 9 µJ (12.98 ± 2.76) was significantly higher than in the 3 µJ (8.54 ± 2.38) and 6 µJ (8.82 ± 2.85) FL energies. Scanning electron microscopy (SEM) images revealed that the corneal stromal surface of the knife incision was smoother than that of the FL. Higher energy FL showed more irregular surfaces. CONCLUSION: Higher FL energy tended to widen a clear corneal incision when mechanical stress was applied. The histological differences at the inner tunnel surface may cause differences in wound stability of the corneal incision.

Effect of Background Luminance Level on the Assessment of Color Visual Acuity Using Colored Landolt Rings in Young Healthy Subjects.

PURPOSE: To evaluate the color visual acuity (CVA) of young healthy subjects using colored Landolt rings and the effect of background luminance level on the CVA. MATERIALS AND METHODS: We measured the CVA of 20 young healthy subjects (age: 23.8 ± 3.8 years) with different colors using a computer and a liquid crystal display, with 15 Landolt ring colors (30 cd/m2) with a background luminance of 30 cd/m2, and then 100 cd/m2. We then used different background luminance levels (15-50 cd/m2) using four Landolt ring colors (red, green-yellow, green, and blue-green) to evaluate the effect of the background luminance level on CVA. RESULTS: The CVA significantly differed among the colors with a background luminance of 30 cd/m2 (p < 0.0001). Green-yellow and blue-purple had poor CVA (high LogMAR value; 0.808 ± 0.107 and 0.633 ± 0.150, respectively) with a background luminance of 30 cd/m2 (same luminance as the Landolt rings). There were no significant differences in the CVAs among the colors with a background luminance of 100 cd/m2 (p = 0.5999). There were no significant difference in the CVA between background luminance 30 cd/m2 and other luminance level ranging from 28 to 32 cd/m2 for colors of red, green-yellow, green, and blue-green. CONCLUSIONS: The results reveal that the background luminance of Landolt rings affects the CVA. Distinctive CVAs for each color are measured by equalizing the luminance between the Landolt ring and the background. We consider that the poor CVAs of these colors reflect the visual function of S-cone, because GY and BP are included in the confusion locus of tritan axis on the chromaticity diagram. We believe that CVA assessment may be useful for individuals who have known or suspected ocular dysfunction or color vision deficiencies.

Comparison of Maximum Stretch Forces between Femtosecond Laser-Assisted Capsulotomy and Continuous Curvilinear Capsulorhexis.

The current study reports comparing the postoperative mechanical properties of the anterior capsule between femtosecond laser capsulotomy (FLC) and continuous curvilinear capsulorhexis (CCC) of variable size and shape in porcine eyes. All CCCs were created using capsule forceps. Irregular or eccentric CCCs were also created to simulate real cataract surgery. For FLC, capsulotomies 5.3 mm in diameter were created using the LenSx® (Alcon) platform. Fresh porcine eyes were used in all experiments. The edges of the capsule openings were pulled at a constant speed using two L-shaped jigs. Stretch force and distance were recorded over time, and the maximum values in this regard were defined as those that were recorded when the capsule broke. There was no difference in maximum stretch force between CCC and FLC. There were no differences in circularity between FLC and same-sized CCC. However, same-sized CCC did show significantly higher maximum stretch forces than FLC. Teardrop-shaped CCC showed lower maximum stretch forces than same-sized CCC and FLC. Heart-shaped CCC showed lower maximum stretch forces than same-sized CCC. Conclusively, while capsule edge strength after CCC varied depending on size or irregularities, FLC had the advantage of stable maximum stretch forces.

[Investigation of Administration Technique of Regorafenib in Our Center].

Regorafenib is an oral multikinase inhibitor; the CORRECTtrial evaluated its efficacy in patients with metastatic colorectal cancer following disease progression with standard therapies. However, regorafenib has toxicities that develop quickly. Few studies have reported the safe dose and usage of regorafenib to avoid these adverse events in Japanese patients. We examined the side effects and safe administration technique of regorafenib in this study. We administered regorafenib to 15 patients with metastatic colorectal cancer following disease progression with standard therapies. Between August 2013 and January 2014, 5 patients received 160 mg oral regorafenib once daily on days 1-21 of a 28 day course(group A). Between February 2014 and July 2015, 10 patients received initiating therapy with 120 mg regorafenib, with the intention of increasing the dose(group B). We retrospectively assessed side effects, number of dose courses, and total dose of regorafenib in both groups. The median dosing course was 5 coureses in group B, which was more than the 1 course in group A. The median total dose was 10,800 mg in group B, which is about 4 times as much as the 2,400 mg in group A. In group B, 7 out of 10 patients (70%)were successful in the dose escalation of regorafenib from 120 to 160 mg daily over 3-5 courses. The disease control rate was 40% in both groups. The rate of adverse events of Grade 3 or higher was 60% in group A, compared to 40% in group B within 2 courses. The overall survival time was 308 days in group B, which was significantly longer than the 168 days in group A. Initiating therapy with 120 mg regorafenib with the intention of increasing the dose improves safety and allows an increase in dosing courses, as well as in the total dose of regorafenib and overall survival time.

Effects of an Oral Elemental Nutritional Supplement on Post-gastrectomy Body Weight Loss in Gastric Cancer Patients: A Randomized Controlled Clinical Trial.

BACKGROUND: Post-gastrectomy weight loss is associated with deterioration in quality of life, and influences the long-term prognosis of gastric cancer patients. We conducted a prospective, randomized controlled, open-label study to examine whether an oral elemental diet (Elental(®), Ajinomoto Pharmaceuticals, Tokyo, Japan; hereafter referred to as ED) prevents postoperative weight loss in post-gastrectomy patients. METHODS: Patients were randomly divided to receive the ED or control diet. The ED group received 300 kcal of ED plus their regular diet for 6-8 weeks after surgery, starting from the day the patient started a soft rice or equivalent diet after surgery, while the control group received the regular diet alone. The primary endpoint was the percentage of body weight loss (%BWL) from the presurgical body weight to that at 6-8 weeks after surgery. Secondary endpoints were dietary adherence, nutrition-related blood parameters, and adverse events. RESULTS: This study included 112 patients in eight hospitals. The mean treatment compliance rate in the ED group was 68.7 ± 30.4 % (median 81.2 %). The %BWL was significantly different between the ED and control groups (4.86 ± 3.72 vs. 6.60 ± 4.90 %, respectively; p = 0.047). In patients who underwent total gastrectomy, the %BWL was significantly different between the two groups (5.03 ± 3.65 vs. 9.13 ± 5.43 %, respectively; p = 0.012). In multivariate analysis, ED treatment, surgery type, and preoperative performance status were independently associated with %BWL. No significant differences were observed in the other clinical variables. CONCLUSIONS: ED supplementation reduced postoperative weight loss in gastric cancer patients undergoing gastrectomy.

[Tolerability of XELOX in postoperative adjuvant chemotherapy for colorectal cancer].

A regimen of capecitabine plus oxaliplatin(XELOX)has become one of the standard postoperative adjuvant chemotherapies for colon cancer. However, few tolerability studies have been conducted in Japan. In this study, we retrospectively examined treatment continuation and the adverse events that occurred during 8 courses of postoperative adjuvant chemotherapy with XELOX in 21 patients with colorectal cancer who had undergone curative resection. The completion rate for 8 courses of treatment with XELOX was 71.4%, while the median relative dose intensities of capecitabine and oxaliplatin were 85.0% and 75.0%, respectively. Although the incidence of subsequent Grade 3 or higher hand-foot syndrome was 14.3%, the rate of peripheral neuropathy was 0%. Our hospital had a high rate of XELOX treatment continuation, suggesting that XELOX adjuvant chemotherapy would be well tolerated in clinical practice as well.

Evaluation of SLC20A2 mutations that cause idiopathic basal ganglia calcification in Japan.

OBJECTIVE: To investigate the clinical, genetic, and neuroradiologic presentations of idiopathic basal ganglia calcification (IBGC) in a nationwide study in Japan. METHODS: We documented clinical and neuroimaging data of a total of 69 subjects including 23 subjects from 10 families and 46 subjects in sporadic cases of IBGC in Japan. Mutational analysis of SLC20A2 was performed. RESULTS: Six new mutations in SLC20A2 were found in patients with IBGC: 4 missense mutations, 1 nonsense mutation, and 1 frameshift mutation. Four of them were familial cases and 2 were sporadic cases in our survey. The frequency of families with mutations in SLC20A2 in Japan was 50%, which was as high as in a previous report on other regions. The clinical features varied widely among the patients with SLC20A2 mutations. However, 2 distinct families have the same mutation of S637R in SLC20A2 and they have similar characteristics in the clinical course, symptoms, neurologic findings, and neuroimaging. In our study, all the patients with SLC20A2 mutations showed calcification. In familial cases, there were symptomatic and asymptomatic patients in the same family. CONCLUSION: SLC20A2 mutations are a major cause of familial IBGC in Japan. The members in the families with the same mutation had similar patterns of calcification in the brain and the affected members showed similar clinical manifestations.

[A case of metachronous triple cancer treated with a multimodal approach including surgical resection].

We report a patient with metachronous triple cancer of the hypopharynx, esophagus, and tongue. A 37-year-old man with hypopharyngeal cancer underwent hypopharyngolaryngectomy and cervical lymphadenectomy in 1999. Submental lymphadenectomy following adjuvant radiotherapy was performed for lymph node recurrence in 2000. The patient then underwent esophagectomy for esophageal cancer in 2004. Subsequently, the patient underwent 2 partial resections and 1 subtotal resection of the tongue for tongue cancer in 2005, 2007, and 2008, respectively. The pathological findings for each cancer were squamous cell carcinoma. Two rounds of radiotherapy were performed for bone metastasis of the esophageal cancer and for the local recurrence of the tongue cancer. A total of 7 lines of chemotherapy, including superselective arterial infusion chemotherapy, were administered to treat the recurrences. The patient died in 2013, but he showed long-term survival of 13 years from the first operation owing to the multimodality treatment.

[Chemotherapy for gastric cancer patients over 75 years of age].

PURPOSE: The efficacy of chemotherapy for advanced or recurrent gastric cancer in patients who were aged over 75 years was investigated. MATERIALS AND METHODS: Progression free survival (PFS) and overall survival (OS) of advanced gastric cancer patients who received first-line chemotherapy with TS-1 plus cisplatin or TS-1 in our hospital from 2009 to 2013 were determined. The patients were divided into two groups: H and L. H group patients were aged over 75 years, and L group patients were aged less than 75 years. RESULTS: Median PFS and median OS of patients in the H and L groups who received TS-1 plus cisplatin chemotherapy were not significantly different. PFS was 77[range, 13-211] days and 139[range, 53-211]days for the H and L groups, respectively(p=0.141), while OS was 523[range, 22-1,030] days and 402 [range, 322-623] days, respectively (p=0.620). Similarly, median PFS and median OS of patients who received TS-1 chemotherapy were not significantly different between the H and L groups. PFS was 103[range, 51-156]days and 152.5[range, 85-278]days for the H and L groups, respectively (p=0.230), while OS was 414 [range, 224-714]days and 605[range, 452-1,077] days, respectively ( p=0.1337). CONCLUSION: PFS and OS were not significantly different in younger patients with advanced gastric cancer who received TS-1 plus cisplatin or TS-1 chemotherapy compared to that in similarly treated elderly patients with advanced gastric cancer.

[A case of advanced gastric cancer successfully treated with second-line chemotherapy followed by curative conversion gastrectomy].

We report a case of advanced gastric cancer that was successfully treated with second-line chemotherapy followed by curative conversion gastrectomy. The patient was a 71-year-old man. Endoscopic examination revealed a type 3 gastric cancer in the lower third of the stomach. Abdominal computed tomography (CT) revealed multiple lymph node metastases and metastasis to the peritoneal cavity. The clinical diagnosis was cT4N3aP1H0M1(LYM), cStage IV. The patient was treated with S-1 (80 mg/m² on days 1-28, every 6 weeks [q6w]) in November 2009. Temporarily, both the size of the primary lesion and the swelling of the lymph nodes were markedly reduced. However, after 10 courses of chemotherapy, the primary lesion was found to be enlarged again. The patient was then treated with S-1(80 mg/m², on days 1-14, every 6 weeks [q3w]) plus CPT- 11 (150 mg/m² on day 1, q3w) as the second-line chemotherapy. After 8 courses, an abdominal CT showed no peritoneal or lymph node metastases, but gastric endoscopy revealed the presence of a residual primary lesion. After staging laparoscopy, distal gastrectomy with D2 lymphadenectomy was performed. The histological diagnosis was ypT3 (SS) N1M0, Stage IIB. Analysis of the histological features of the primary tumor and peritoneal metastases resulted in their classifications as Grade 1a and Grade 3, respectively. After surgery, there were no serious adverse events. The patient has been in good health without recurrence for over 3 years after surgery.

Localization of type-III sodium-dependent phosphate transporter 2 in the mouse brain.

Type-III sodium-dependent phosphate transporters 1 and 2 (PiT-1 and PiT-2, respectively) are proteins encoded by SLC20A1 and SLC20A2, respectively. The ubiquitous distribution of PiT-1 and PiT-2 mRNAs in mammalian tissues is in agreement with the housekeeping maintenance of homeostasis of intracellular inorganic phosphate (Pi), which is absorbed from interstitial fluid for normal cellular functions. Recently, mutations of SLC20A2 have been found in patients with idiopathic basal ganglia calcification (IBGC), also known as Fahr's disease. However, the localization of PiT-2 in the brain has not been clarified yet. Therefore, the aim of this study is to clarify the distribution of PiT-2 expression in the mouse brain. Our biochemical and immunohistochemical analyses using a polyclonal antibody (Ab) and a monoclonal Ab showed that PiT-2 was ubiquitously expressed throughout the brain. In terms of the cellular type, PiT-2 was predominantly detected in neurons; it colocalized with ß-tubulin III in the cerebral cortex and with calbindin D-28K in Purkinje cells. Additionally, PiT-2 immunopositivity was detected in the microtubule-associated protein 2-positive neuronal dendrites in the cerebral cortex. However, colocalization with PiT-2 immunopositivity was not observed in the synaptophysin-positive nerve terminals. PiT-2 was also expressed in astrocytes and vascular endothelial cells. Our results indicate that PiT-2 plays an important role in the maintenance of cellular Pi homeostasis in neurons, astrocytes, and endothelial cells. This finding is a milestone in the study of the function of PiT-2 in the normal mouse brain and particularly in the brains of patients with Fahr's disease.

[Study of tolerability of capecitabine in postoperative adjuvant chemotherapy in colon cancer].

OBJECTIVE: Based on the results of the X-ACT study, capecitabine has become one of the standard postoperative adjuvant chemotherapies for colon cancer. However, few studies of tolerability have been conducted in Japan. METHOD: In this study, we retrospectively examined treatment continuation, and the adverse events that occurred during eight courses of postoperative adjuvant chemotherapy with capecitabine, in 34 patients with colon cancer who had undergone curative resection. RESULT: The completion rate for eight courses of treatment with capecitabine was 79. 4%(27 of 34 subjects), the median relative dose intensity was 94. 4%(13% to 106%), and the proportion of subjects with relative dose intensity B 60% was 82. 4%(28 of 34 subjects). The following Grade 3 or higher adverse events were reported: hand-foot syndrome, in 11. 8%(4 of 34 subjects); mucositis oral, in 2. 9%(1 of 34 subjects); diarrhea, in 2. 9%(1 of 34 subjects); and glans penis ulcer, in 2. 9%(1 of 34 subjects). CONCLUSION: In our hospital, a high rate of capecitabine treatment continuation comparable to that reported in the X-ACT study was obtained, suggesting that capecitabine adjuvant chemotherapy would be well tolerated in clinical practice as well.

Efficient production of recombinant cystatin C using a peptide-tag, 4AaCter, that facilitates formation of insoluble protein inclusion bodies in Escherichia coli.

Cystatin C is a cysteine protease inhibitor produced by a variety of human tissues. The blood concentration of cystatin C depends on the glomerular filtration rate and is an endogenous marker of renal dysfunction. Recombinant cystatin C protein with high immunogenicity is therefore in demand for the diagnostic market. In this study, to establish an efficient production system, a synthetic cystatin C gene was designed and synthesized in accordance with the codon preference of Escherichia coli genes. Recombinant cystatin C was expressed as a fusion with a peptide-tag, 4AaCter, which facilitates formation of protein inclusion bodies in E. coli cells. Fusion with 4AaCter-tag dramatically increased the production level of cystatin C, and highly purified protein was obtained without the need for complicated purification steps. The purity and yield of the final product was estimated as 87 ± 5% and 7.1 ± 1.1 mg/l culture, respectively. The recombinant cystatin C prepared by our method was as reactive against anti-cystatin C antibodies as native human cystatin C. Our results suggest that protein production systems using 4AaCter-tag could be a powerful means of preparing significant amounts of antigen protein.

[Efficacy of capecitabine/cisplatin chemotherapy after failure of all conventional therapies in patients with advanced gastric cancer].

There is no standard therapy for advanced gastric cancer patients who had already failed treatment with major anti-cancer drugs including fluoropyrimidine, cisplatin, taxans, and irinotecan. We report the results of treatment with capecitabine and cisplatin(XP)after the failure of all other conventional therapies. A total of five advanced gastric cancer patients were treated. The median age was 59 years(range, 46-76); there were 3male and 2 female patients; performance status was 0/1/2: 2/2/ 1 patients, respectively. The median duration from start of first-line chemotherapy to XP was 653 days(range, 372-1,107). Three patients were treated after fourth-line therapy and two patients after fifth-line therapy. All of the patients had received S-1, cisplatin, irinotecan, paclitaxel, and docetaxel previously. Patients received 80mg/m2 of cisplatin intravenously on day 1, and 1,000mg/m2 of capecitabine orally twice a day from day 1 to day 14 followed by a 7-day rest period. Treatment courses were between 2 to 5. Median time to progression was 107 days. Median overall survival was 245 days. One PR and one SD were reported. All reported adverse events were manageable. XP is considered one of the effective regimens for advanced gastric cancer after all conventional therapies have failed.

Decreased bioelements content in the hair of patients with Fahr's disease (idiopathic bilateral calcification in the brain).

The remarkable calcification of the basal ganglia and cerebellum has been traditionally called Fahr's disease, but this nomenclature is criticized for including heterogeneous diseases. To determine the pattern of some biological metals in the hair of patients with Fahr's disease, we investigated the levels of 24 bioelements in the hair of 28 patients (17 males and 11 females) with Fahr's disease and compared them with those of three age-, sex-, and living region-matched controls (84 controls in total). Interestingly, we found decreases in the levels of several bioelements [calcium (Ca), copper (Cu), iron (Fe), mercury (Hg), iodine (I), nickel (Ni), phosphate (P), lead (Pb), and selenium (Se)] in the hair of patients. This is in contrast to our previous finding of increases of Cu, Fe, zinc (Zn), and magnesium (Mg) in the cerebrospinal fluid (CSF) of patients. The decreased level of Cu in the hair was the most prominent and pathognomonic, while the increased level of Cu in the CSF had been found to be the most significant in patients. More significant correlations between two bioelements in the hair were recognized in patients than controls. Although Fahr's disease has been considered to be a heterogenous entity, the significant tendencies of several bioelements in the hair of patients in this study suggest metabolic disorders of bioelements, especially biometals, on the background. Some transporters, especially P transporter such as PiT2, of bioelements will be involved in the different distribution of bioelements in the body of patients.