The significance of CA-50, SLX and ST-439 in lung cancer]

Serum levels of CA-50, SLX and ST-439 were measured in 213 patients with lung cancer (92 adenocarcinomas, 63 squamous cell carcinomas, 37 small cell carcinomas and 21 large cell carcinomas) and 87 patients with benign lung disease. The overall positive rates in patients with lung cancer were 12.8% for CA-50, 29.7% for SLX and 25.3% for ST-439. The positive rates for CA-50, SLX and ST-439 in adenocarcinoma patients were 22.8%, 42.4% and 38.0%, respectively. Of the patients with benign lung disease, 4.8% were false positive for CA-50, 15.3% for SLX and 3.6% for ST-439. In the patients with adenocarcinoma of the lung, the combination assay of CEA and ST-439 had a highly accurate rate (61.9%).     

Phase I and pharmacologic study of oral (E)-2′-deoxy-2′-(fluoromethylene) cytidine: on a daily × 5-day schedule

(E)-2-deoxy-2-(fluoromethylene)cytidine (FMdC), one of the most potent inhibitors of ribonucleoside diphosphate reductase, was selected for clinical development because of its novel mechanisms of action, and strong antitumor activity against experimental tumor models. This study was designed to determine the toxicities, maximum-tolerated dose (MTD), and pharmacokinetic profile of FMdC. FMdC was given orally for 5 consecutive days every 3 or 4 weeks in patients with advanced solid tumors. The starting dose was 8 mg/m2/day. Pharmacokinetic studies were carried out on days 1 through 5 of the first cycle. Ten patients with non-small cell lung cancer received 15 courses of FMdC at doses which were de-escalated from 8 mg/m2/day to 2 mg/m2/day because of unexpected severe toxicities at the starting dose level. Neutropenia was the dose-limiting toxicity. Thrombocytopenia and anemia were mild. Flu-like symptoms and fever were the common non-hematologic toxicities. The MTD was 4 mg/m2/day, since four of six patients developed grade 3–4 neutropenia. At the 4 mg/m2/day dose level, the mean terminal half-life, maximum plasma concentration (Cmax), plasma clearance, and mean residence time on day 1 were 3.20 h, 15.8 ng/ml, 2.91 l/h/kg, and 4.03 h, respectively. The recommended dose for phase II studies with this schedule is also 4 mg/m2/day for 5 days. Further investigations are necessary to establish optimal dosing schedules and routes for the administration of FMdC.     

Overexpression of cyclin‐dependent kinase 4 protein in extramammary Paget's disease

Cyclin‐dependent kinase 4 and 6 (CDK4/6) plays an important role in cell cycle progression, and the CDK4/6–cyclin D1 complex controls the cell cycle transition from G₁ phase to S phase. CDK4 is enhanced in several types of cancers and CDK4/6 inhibitors attenuate the proliferation of several types of cancer in vitro/in vivo. The purpose of our study was to investigate the expression pattern of CDK4 and evaluate its clinical importance in extramammary Paget's disease (EMPD). Almost all EMPD tissues were positive for CDK4, and metastatic lesions had a similar immunostaining intensity to primary lesions. In addition, CDK4 protein levels were positively correlated with those of cyclin D1 protein. Taken together, CDK4 may assume a crucial role in EMPD progression.     

Estimated Daily Intake and Seasonal Food Sources of Quercetin in Japan

Quercetin is a promising food component, which can prevent lifestyle related diseases. To understand the dietary intake of quercetin in the subjects of a population-based cohort study and in the Japanese population, we first determined the quercetin content in foods available in the market during June and July in or near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained high amounts of quercetin derivatives. We then estimated the daily quercetin intake by 570 residents aged 20–92 years old in the town using a food frequency questionnaire (FFQ). The average and median quercetin intakes were 16.2 and 15.5 mg day⁻¹, respectively. The quercetin intakes by men were lower than those by women; the quercetin intakes showed a low correlation with age in both men and women. The estimated quercetin intake was similar during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good sources of quercetin in summer. Our results will help to elucidate the association between quercetin intake and risks of lifestyle-related diseases by further prospective cohort study and establish healthy dietary requirements with the consumption of more physiologically useful components from foods.     

Primary anaplastic large cell lymphoma of the psoas muscle: a case report and literature review

Primary anaplastic large cell lymphoma (ALCL) of skeletal muscle is very rare. We report a case of ALCL arising from the left psoas muscle. A 14-year-old girl presented with a large left inguinal tumor. She complained of a 2-month history of left leg pain, which had been exacerbated upon leg extension, and she had become aware of a rapidly growing left inguinal tumor 3 weeks before admission. CT scan and MRI revealed a large tumor arising from the left major psoas muscle and protruding into the inguinal region. In view of the tumor's location and the patient's age, soft tissue tumors such as rhabdomyosarcoma and primitive neuroectodermal tumor were initially considered. However, histopathological examination yielded a diagnosis of anaplastic lymphoma kinase-positive ALCL. The serum level of soluble interleukin-2 receptor was markedly elevated at 50,414 U/ml, and this also strongly suggested ALCL. Although rarely reported, ALCL is an important entity to consider in the differential diagnosis of skeletal muscle tumors in children and young adults.     

Clinical outcome of up-front surgery in patients with asymptomatic, incurable synchronous peritoneal carcinomatosis

Purposes

The purpose of this study was to show the clinical features of up-front surgery of the primary tumor in asymptomatic patients with incurable colorectal PC.

Methods

Forty-six patients that were diagnosed between 1998 and 2007 with asymptomatic colorectal PC who could not be successfully cured by surgery were assessed retrospectively.

Results

A univariate analysis revealed the presence of liver metastases, without the use of oxaliplatin (OX)/irinotecan (IRI) and without a primary tumor resection to be poor prognostic factors for survival (p = 0.044, p = 0.030, p < 0.001, respectively). According to a multivariate analysis, no use of OX/IRI and no primary tumor resection, were found to be independent poor prognostic factors for survival (HR 2.57; p = 0.047, HR 6.62; p = 0.003, respectively). The median survival time of patients treated with and without OX/IRI was 18 and 7 months, respectively. The median survival time of patients with and without primary tumor resection was 10 and 2 months, respectively. The number of patients needing surgical intervention for intestinal obstruction after surgery significantly increased in patients treated with OX/IRI (p = 0.001).

Conclusion

Improvement of survival may be related to widespread use of modern systemic chemotherapy and primary tumor resection. However, an increased number of patients that needed surgery for an intestinal obstruction were observed, even after up-front surgery, when patients were treated with modern systemic chemotherapy.     

Diagnosis of nail psoriasis: evaluation of nail-derived microRNAs as potential novel biomarkers

Background

MicroRNA levels in sera or hair may potentially be useful biomarkers for various diseases. The diagnosis of nail diseases is sometimes difficult, and nail psoriasis without skin lesions is indistinguishable from nail changes caused by other diseases.

Objectives

We evaluated nail microRNA levels as biomarkers for the diagnosis of psoriasis patients.

Materials & methods

MicroRNA levels were examined in psoriasis patients with (11 patients) and without (six patients) nail changes. Normal control nails were collected from 17 healthy subjects. Eight patients with other diseases who also had nail changes were also included as disease controls.

Results

Microarray, real-time PCR, and in situ hybridisation indicated that the expression levels of nail miR- 4454 were decreased in psoriasis patients with nail changes, compared to those patients with other diseases involving nail change, or healthy subjects. The miR-4454 levels in nails showed a significant inverse correlation with the Nail Psoriasis Severity Index (NAPSI) score, suggesting that nail miR-4454 levels reflect nail condition.

Conclusion

The levels of microRNAs in nails may be suitable biomarkers for diagnosis or evaluation of disease activity of psoriasis.

     

Relationship between the Pharmacokinetics of Irinotecan and Diarrhea during Combination Chemotherapy with Cisplatin

Two phase I trials of irinotecan (CPT-11) in combination with cisplatin were conducted. In both cases, the dose-limiting toxicities were leukopenia and/or diarrhea. During these trials the pharmacokinetics of CPT-11 and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), were investigated to evaluate the relationship between pharmacokinetic parameters and diarrhea, since this is an unpredictable and severe toxicity of combination chemotherapy using CPT-11 and cisplatin. Twenty-three previously untreated patients with advanced lung cancer were evaluated in the pharmacokinetic study. Ten patients received CPT-11 at 80 or 90 mg/m² plus cisplatin at 60 mg/m². The other 13 patients received CPT-11 at 80 or 90 mg/m² plus cisplatin at 80 mg/m² with the granulocyte colony-stimulating factor support (2 μg/kg × 16 days). CPT-11 was given as a 90-min intravenous infusion on days 1, 8, and 15. Cisplatin was given on day 1. The pharmacokinetics of CPT-11 and SN-38 were analyzed on day 8 during the first course of treatment. The maximum tolerated dose of CPT-11 was 90 mg/m² in both phase I trials. The severity of diarrhea was best correlated with the peak plasma concentration of SN-38 among the pharmacokinetic parameters tested. In addition, patients with a plasma SN-38 level > 12.4 ng/ml at 1.75 h after the start of CPT-11 infusion had a higher incidence of Eastern Cooperative Oncology Group grade 3–4 diarrhea than those with a lower SN-38 level ( P =0.0003). Stepwise logistic regression analysis identified the SN-38 concentration as a significant contributor to the development of diarrhea ( P =0.0021). We conclude that there is a clear relationship between the SN-38 concentration and diarrhea during chemotherapy with CPT-11 plus cisplatin.