Screening of a heptamer-type sgRNA library for potential therapeutic agents against hematological malignancies.

tRNase-Z(L)-utilizing efficacious (TRUE) gene silencing is an RNA-mediated gene expression control technology that has therapeutic potential. This technology is based on the property of tRNase Z(L) that it can cleave any target RNA at any desired site under the direction of an appropriate artificial small guide RNA (sgRNA). To search for novel potential therapeutic sgRNAs for hematological malignancies, we screened a library composed of 156 sgRNAs, and found that 20 sgRNAs can efficiently induce apoptosis in leukemia and/or myeloma cells.

Hepatic arterial infusion chemotherapy with cisplatin before radical local treatment of early hepatocellular carcinoma (JIS score 0/1) improves survival.

Background: It has not yet been determined whether hepatic arterial infusion (HAI) chemotherapy improves survival in patients with early hepatocellular carcinoma (HCC). We evaluated the effectiveness of HAI with high-concentration cisplatin (DDP-H) for the treatment of HCC by comparing outcomes between patients who received HAI with DDP-H before radical local treatment of early-stage HCC [Japan Integrated Staging (JIS) score 0/1] and patients who did not receive HAI chemotherapy.

Patients And Methods: Survival was analyzed in 114 patients with early-stage HCC who underwent radical local treatment.

[Safety of axillary and subclavian vein cannulation using real-time ultrasound guidance].

Background: The safety of real-time ultrasound-guided subclavian and axillary vein cannulation as opposed to ultrasound-guided internal jugular vein cannulation has not received much attention. We retrospectively compared the safety and value of real-time ultrasound-guided cannulation in the subclavian and axillary veins with those of the landmark method.

Methods: We divided 355 patients who had undergone central venous cannulation of the subclavian and axillary vein under local anesthesia into a group that had undergone real-time ultrasound-guided cannulation (Group U), and another group cannulated using the landmark method (Group L).

Anti-viral therapy to reduce recurrence and improve survival in hepatitis B virus-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common malignancy and the third leading cause of cancer death worldwide. Chronic infection with hepatitis B virus (HBV) and hepatitis C virus accounts for approximately 75%-80% of HCC cases worldwide. In particular, chronic HBV infection is a predominant risk factor for HCC in Asia and Africa.

Strategy for improving survival and reducing recurrence of HCV-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death in the world. With advances in imaging diagnostics, accompanied by better understanding of high-risk patients, HCC is now frequently detected at an early stage; however, the prognosis remains poor. The recurrence rate after treatment of HCC is higher than that associated with cancers of other organs.

Concurrent partial splenic embolization with transcatheter arterial chemoembolization for hepatocellular carcinoma can maintain hepatic functional reserve.

Aim: Hepatocellular carcinoma (HCC) is frequently complicated with cirrhosis, and it is not unusual for treatment options to be limited as a result of pancytopenia due to hypersplenism. Partial splenic embolization (PSE) has been performed for thrombocytopenia resulting from hypersplenism. We studied the efficacy in terms of hepatic functional reserve and safety in patients who underwent concurrent transcatheter arterial chemoembolization (TACE) with PSE for HCC.

Radiofrequency ablation during continuous saline infusion can extend ablation margins.

Aim: To determine whether fluid injection during radiofrequency ablation (RFA) can increase the coagulation area.

Methods: Bovine liver (1-2 kg) was placed on an aluminum tray with a return electrode affixed to the base, and the liver was punctured by an expandable electrode. During RFA, 5% glucose; 50% glucose; or saline fluid was infused continuously at a rate of 1.

Surfactant protein-D is more useful than Krebs von den Lungen 6 as a marker for the early diagnosis of interstitial pneumonitis during pegylated interferon treatment for chronic hepatitis C.

Background/aims: To examine the usefulness of serum Krebs von den Lungen 6 (KL-6) and surfactant protein-D (SP-D) as markers of interstitial pneumonitis. Many antiviral therapies have become available for chronic hepatitis C, including pegylated interferon (PEGIFN) plus ribavirin. Since interstitial pneumonitis is a serious adverse drug reaction during interferon therapy, interferon treatment requires caution in respiratory disease patients.

Histopathology of the tissue adhering to the multiple tine expandable electrodes used for radiofrequency ablation of hepatocellular carcinoma predicts local recurrence.

Objective: To assess the ability to predict the local recurrence of hepatocellular carcinoma by analyzing tissues adhering to the radiofrequency ablation probe after complete ablation.

Methods: From May 2002 to March 2011, tissue specimens adhering to the radiofrequency ablation probe from 284 radiofrequency ablation sessions performed for hepatocellular carcinomas ≤3 cm in size were analyzed. The specimens were classified as either viable tumor tissue or complete necrosis, and the local recurrence rates were calculated using the Kaplan-Meier method.

Early administration of branched-chain amino acid granules.

The effect of malnutrition on survival in patients with decompensated liver cirrhosis has not been well defined. Nutritional intervention with branched-chain amino acid (BCAA) can increase serum albumin concentration in patients with decompensated cirrhosis but its effects on survival are unclear. The BCAA to tyrosine ratio (BTR) is a surrogate marker (the normal range of BTR is between 4.

Can zinc enhance response interferon therapy for patients with HCV-related liver disease?

Patients with liver disease may be at risk of zinc depletion. Zinc supplementation has been shown to contribute to inhibition of liver fibrosis and improvement in hepatic encephalopathy. However, little is known about the anti-inflammatory effect of zinc on hepatitis C virus (HCV)-related chronic liver disease.

Branched-chain amino acids to tyrosine ratio value as a potential prognostic factor for hepatocellular carcinoma.

The prognosis of hepatocellular carcinoma (HCC) depends on tumor extension as well as hepatic function. Hepatic functional reserve is recognized as a factor affecting survival in the treatment of HCC; the Child-Pugh classification system is the most extensively used method for assessing hepatic functional reserve in patients with chronic liver disease, using serum albumin level to achieve accurate assessment of the status of protein metabolism. However, insufficient attention has been given to the status of amino acid (AA) metabolism in chronic liver disease and HCC.

Efficacy of the regimen using twice-daily β-interferon followed by the standard of care for chronic hepatitis C genotype 1b with high viral load.

Aim:   In patients with refractory genotype 1b chronic hepatitis C with high viral loads, we retrospectively compared the efficacy of standard of care treatment (SOC: combined PEG-IFN-α-2b/ribavirin for 48 weeks) and a regimen in which 2 weeks of SOC induction was replaced by twice-daily β-interferon alone (IFN-β induction therapy).

Methods:   Seventeen patients received the IFN-β induction therapy plus SOC (IFN-β induction group) and 13 patients received SOC alone (SOC group).

Results:   In the IFN-β induction group and SOC group, early virological response (EVR) rates were 88.

Complete early virological response was highly achieved by double filtration plasmapheresis plus IFN-beta induction therapy for HCV-1b patients with relapse or no response after previous IFN therapy.

The efficacy of double filtration plasmapheresis (DFPP) plus interferon (IFN)-β induction therapy was preliminarily investigated in re-treated patients with chronic genotype 1b hepatitis C and high viral load (patients with relapse or non-response to previous IFN therapies). In eight patients with chronic hepatitis C, DFPP was performed five times over 2 weeks during IFN-β therapy, and 3 MU of IFN-β was administered twice a day for 2 weeks. Combination therapies with ribavirin and pegylated IFN-α2b (PEG-IFN-α2b) or pegylated IFN-α2a (PEG-IFN-α2a) were subsequently used.

Prevention of intrahepatic distant recurrence by transcatheter arterial infusion chemotherapy with platinum agents for stage I/II hepatocellular carcinoma.

Background: The effectiveness of additional chemotherapy in preventing intrahepatic distant tumor recurrence of hepatocellular carcinoma (HCC) has not been fully established. The authors compared the efficacy of 2 platinum-based chemotherapeutic agents in combination with radical local treatment for preventing intrahepatic distant recurrence (IDR).

Methods: Seventy-eight patients with stage I/II HCC aged 45 to 85 years underwent transcatheter arterial chemoembolization and/or radiofrequency ablation after they received hepatic arterial infusion (HAI) of platinum compounds.

Clinical value of assessing the response to imatinib monitored by interphase FISH and RQ-PCR for BCR-ABL in peripheral blood for long-term survival of chronic phase CML patients: results of the Niigata CML-multi-institutional co-operative clinical study.

This retrospective analysis investigated the prognostic value of monitoring the response to imatinib using peripheral blood (PB) samples and the impact of the response on outcome in 133 patients with chronic myeloid leukemia (CML). We divided the response into 3 categories according to the results of neutrophil (N)-FISH and BCR-ABL transcript levels in PB; more than a 3-log reduction [major molecular response (MMR)], between a 2-log and 3-log reduction or negative with N-FISH [complete cytogenetic response equivalent (CCyRe)], N-FISH positive or less than a 2-log reduction (non-CCyRe). The median follow-up was 5.

Evaluation of dosing time-related anti-hypertensive efficacy of valsartan in patients with type 2 diabetes.

The aim of this study was to evaluate which administration timing of valsartan provides satisfactory blood pressure (BP) control, once daily in the morning, once daily in the evening, or twice daily in total 160 mg. Hypertensive patients with mild-to-moderate diabetic nephropathy were enrolled, but those with more than three anti-hypertensive agents, renal insufficiency (serum creatinine ≥ 3 mg/ dL), or hepatic insufficiency were excluded. They were randomized to receive valsartan 160mg once daily in the morning, valsartan 160 mg once daily in the evening, or valsartan 80 mg twice daily for 12 weeks according to a three-period crossover design.

[Osteoarthritis of the knee joint as a cause of musculoskeletal ambulation disability symptom complex (MADS)].

Osteoarthritis is considered as a chronic disease of the whole joint, including articular cartilage, meniscus, ligament, and peri-articular muscle that may result from multiple pathophysiological mechanisms. Osteoarthritis is a painful and disabling disease that affects millions of patients. Its aetiology is largely unknown, but is most likely multi-factorial.

[Visual course for proliferative diabetic retinopathy after pars plana vitrectomy].

Purpose: To investigate retrospectively the visual course for proliferative diabetic retinopathy after pars plana vitrectomy.

Cases And Methods: From January 2002 to December 2004, we operated 209 eyes with proliferative diabetic retinopathy. For this study, we selected 28 eyes in which the visual acuity could be followed for 6 months or longer after the vitrectomy.

[Up-date of cartilage repair technique].

There are two major conditions which require cartilage repair, one is partial cartilage defect due to trauma or osteochondritis dissecanse and the other is cartilage degeneration and loss induced by osteoarthritis. In this section, we introduce several surgical techniques which are available in clinical cases. In patient with relatively small traumatic cartilage defect, microfracture technique, autologous osteochondral graft transplantation, or autologous cultured chondrocytes transplantation are performed.

[Optic nerve atrophy after vitrectomy for diabetic retinopathy: its systemic and local risk factors].

Purpose: To evaluate the incidence and risk factors of optic nerve atrophy after vitrectomy for diabetic retinopathy.

Subjects And Methods: Clinical charts of 48 eyes of 40 patients who underwent vitrectomy for diabetic retinopathy were retrospectively reviewed. The relationship between postoperative optic nerve atrophy and patients' physical condition was statistically analyzed.