Scent test using Caenorhabditis elegans to screen for early-stage pancreatic cancer

Although early detection and diagnosis are indispensable for improving the prognosis of patients with pancreatic cancer, both have yet to be achieved. Except for pancreatic cancer, other cancers have already been screened through scent tests using animals or microorganisms, including Caenorhabditis elegans. While such a method may greatly improve the prognosis of pancreatic cancer, no studies have investigated the same, mainly given the difficulty of collecting suitable samples from patients with early-stage pancreatic cancer. In this study, we organized a nationwide study group comprising high-volume centers throughout Japan to collect patients with very-early-stage pancreatic cancer (stage 0 or IA). We initially performed an open-label study involving 83 cases (stage 0–IV), with subsequent results showing significant differences after surgical removal in stage 0–IA (×10 dilution: p < 0.001; ×100 dilution: p < 0.001). Thereafter, a blinded study on 28 cases (11 patients with stage 0 or IA disease and 17 healthy volunteers) was conducted by comparing very-early-stage pancreatic cancer patients with healthy volunteers to determine whether C. elegans could detect the scent of cancer for the diagnosis of early-stage pancreatic cancer. Preoperative urine samples had a significantly higher chemotaxis index compared to postoperative samples in patients with pancreatic cancer [×10 dilution: p < 0.001, area under the receiver operating characteristic curve (AUC) = 0.845; ×100 dilution: p < 0.001, AUC = 0.820] and healthy volunteers (×10 dilution: p = 0.034; ×100 dilution: p = 0.088). Moreover, using the changes in preoperative and postoperative chemotaxis index, this method had a higher sensitivity for detecting early pancreatic cancer compared to existing diagnostic markers. The clinical application C. elegans for the early diagnosis of cancer can certainly be expected in the near future.     

Serum CRP and IL-6, genetic variants and risk of colorectal adenoma in a multiethnic population

Chronic inflammation, which is suspected to play a role in the development of colorectal cancer (CRC), has rarely been studied in colorectal adenoma. We investigated the inter-relationships of serum levels of the inflammatory proteins CRP and in IL-6, single nucleotide polymorphisms (SNPs) in the CRP (rs1205, rs1130864, rs1800947) and IL6 (rs1800795) genes, and lifestyle factors with colorectal adenoma in a sigmoidoscopy-based case–control study of 271 adenoma cases and 539 age-, sex-, and race/ethnicity-matched controls in Hawaii. We found no association of serum CRP or IL-6 levels with the risk of adenoma. A multiple regression with stepwise selection identified elevated BMI, Caucasian and Native Hawaiian versus Japanese race/ethnicity, and current smoking as being associated with significantly higher serum CRP and IL-6 levels. Female versus male gender was also associated with higher CRP levels and older age with higher IL-6 levels. The C allele of rs1205 and the A allele of rs1130864 were significantly associated with higher serum CRP levels (p _trend: 0.0002 and 0.01, respectively), as well as with a decreased adenoma risk [rs1205: OR for CT and CC vs. TT = 0.69 (95% CI: 0.48–0.98) and 0.53 (0.34–0.83), respectively, p _trend = 0.008; rs1130864: OR for GA and AA versus GG = 0.65 (0.45–0.93) and 0.74 (0.31–1.76), respectively, p _trend = 0.04]. The findings of lower serum CRP and IL-6 levels in Japanese (a group with a high CRC risk) and of a decreased adenoma risk observed for alleles associated with higher circulating CRP levels suggest a protective effect for CRP in early colorectal neoplasia that warrants further study.     

Experimental verification of age-dependent cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced computed tomography

Purpose  

The aim of this study was to investigate age-dependent cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced computed tomography (DCE-CT).     

A phase II study of 5-fluorouracil/L-leucovorin/oxaliplatin (mFOLFOX6) in Japanese patients with metastatic or unresectable small bowel adenocarcinoma

Background

Several studies have suggested that chemotherapy prolonged survival in patients with metastatic or recurrent small bowel adenocarcinoma (SBA); however, there is still no standard chemotherapy regimen. Here, we evaluated the efficacy and safety of a 5-fluorouracil (5-FU)/L-leucovorin (l-LV)/oxaliplatin (mFOLFOX6) protocol as a first-line therapy for patients with SBA.

Patients and methods

This was a multicenter, single-arm, open-label phase II study. Eligibility criteria included histologically confirmed adenocarcinoma, age 20–80 years, and an Eastern Cooperative Oncology Group performance status (PS) of 0–2. The primary endpoint was 1-year progression-free survival (PFS). The secondary endpoints included overall response rate (ORR), overall survival (OS), overall PFS, and safety.

Results

Between April 2010 and November 2012, 24 patients were enrolled from 12 institutions. The median age of the patients was 63 years (range 31–79) and there was a male/female ratio of 18/6. The number of PS 0/1 patients was 17/7 and locally advanced/metastatic disease was seen in 2/22 patients, respectively. The primary tumor site was the duodenum in 14 patients (58%) and jejunum in 10 patients (42%). The median follow-up time was 14.7 months (3.7–40.3). The 1-year PFS was 23.3%. The ORR was 9/20 (45%). The median PFS and OS times were 5.9 months (95% confidence interval [CI] 3.0–10.2) and 17.3 months (95% CI 11.7–19.0), respectively. Major grade 3/4 toxicities were neutropenia (38%), anemia/peripheral neuropathy (25%), and stenosis (17%). There were no treatment-related deaths.

Conclusions

Although the primary endpoint was not met, mFOLFOX6 showed effective and good tolerance as a first-line treatment for SBA.

     

Premature apoptosis of keratinocytes and the dysregulation of keratinization in porokeratosis

BACKGROUND: Porokeratosis is a dyskeratotic disorder of the skin characterized by cornoid lamella with parakeratosis, hyperkeratosis and loss of granular layers. The pathogenesis of porokeratosis and the mechanism(s) of its abnormal keratinization are still unknown. OBJECTIVE: To elucidate the mechanism(s) of abnormal keratinization that leads to the formation of cornoid lamellae in porokeratosis. METHODS: Apoptosis of keratinocytes was assessed in the skin of seven patients by an in situ apoptosis assay based on the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) reaction. Patterns of loricrin and involucrin expression were examined by immunohistochemistry. RESULTS: TUNEL-positive keratinocytes were observed in the epidermis underlying the cornoid lamella in all cases examined. Furthermore, loricrin expression was interrupted there, in contrast to involucrin, which was expressed diffusely in the lesional epidermis. CONCLUSIONS: These results suggest that an abnormal early keratinocyte apoptosis accompanied by dysregulation of terminal differentiation of those cells may be involved in the pathogenesis of porokeratosis.     

Soluble E-selectin as a marker of disease activity in pustulosis palmaris et plantaris

In this study, we investigated a possible correlation between adhesion molecules and activity of pustulosis palmaris et plantaris (PPP). Serum levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecules 1 (sICAM-1) and tumour necrosis factor alpha (TNF-alpha) in 30 untreated PPP patients were examined, and compared with those in 20 healthy subjects. Values in 10 PPP patients were re-examined after treatment. Serum levels of sE-selectin and TNF-alpha in untreated PPP patients were significantly higher than those in healthy subjects. There was a statistically significant correlation between the disease activity and serum levels of sE-selectin in untreated PPP patients. Furthermore, disease activity of PPP was higher in patients who smoked and during the summer, with elevation of serum sE-selectin levels. Serum levels of sE-selectin were downregulated with the recovery from PPP. These results suggest that sE-selectin may play a role in the pathogenesis of PPP and could be a reliable marker of its disease activity.