Cells of origin and tumor-initiating cells for nonmelanoma skin cancers

The epidermis of the skin is a multilayered stratified epithelium whose primary function is to provide a barrier against our external environment. As a result, cells in the epidermis are subject to constant assault from environmental pathogens, many of which can cause deleterious mutations. However, most of these mutations do not lead to skin cancer. One explanation is that most genetic hits are sustained by mature or transit cells with limited proliferative capacity and only stem cells that acquire genetic alterations have the potential to propagate a frank tumor. In this mini-review we will discuss recent studies that provide some of the first genetic evidence to support a stem cell origin for a number of skin cancer types.     

Diffractive microscopy in dermatopathology

Diffraction is the process by which a beam of light is spread out as a result of passing through a narrow aperture or across an edge. Light diffraction can be produced by closing the aperture diaphragm beyond the recommended setting, by flipping the condenser cone down, or by using an opaque object such as the microscopist's hand to block the column of light and force it to bend around the edge. Any of these techniques results in greater refractility of objects in the path of the light. We studied 77 biopsy specimens from a variety of conditions selected to compare the value of diffractive microscopy, and found that it worked best in the evaluation of alopecia, tumor stroma, hemosiderin, argyria and imipramine pigmentation. In amyloidosis stained with Congo red and silica granuloma, polarized microscopy was superior to diffraction microscopy, and neither diffractive microscopy nor polarized microscopy was superior to routine light microscopy in the evaluation of melanin, chrysiasis or ochronosis.     

Prevalence of intestinal parasitic infections in northern Vietnam

We surveyed the prevalence of parasitic infections in the mountainous province of Hoa Binh, north-west Vietnam, involving 526 households of six ethnic groups: Muong, Kinh, Dao, Thai, Tay and Hmong. Eggs or cysts of at least one parasite species were detected in 88% of stool samples (n = 2522). Prevalences of nematodes were high among all ethnic groups: hookworm (52%), Trichuris trichiura (50%) and Ascaris lumbricoides (45%). Ascaris infection appeared to be lower in households owning a latrine, was highest among children and decreased with age. Prevalence of hookworm rose during childhood, remained high until old age, was highest among adult women, but was not linked to anaemia. Eggs of Chlonorchis spp. were found in 126 (5%) individuals (of the Muong, Kinh or Thai groups only). Chlonorchiasis increased with age and was highest among adult men. Taenia eggs were found in three individuals (0.1%). Giardia lamblia was found in all districts and among all groups and the prevalence of infection was estimated at 3%.     

Infectious titer assay for adeno-associated virus vectors with sensitivity sufficient to detect single infectious events

A highly sensitive assay for determination of infectious titers of recombinant adeno-associated virus (AAV) by limiting dilution analysis is described. This assay is capable of detecting single infectious events and can therefore provide an absolute rather than relative measure of infectivity. The assay utilizes a HeLa-derived AAV2 Rep/Cap-expressing cell line, D7-4, grown in 96-well plates and infected with replicate 10-fold serial dilutions of AAV2 vectors in the presence of adenovirus type 5. Forty-eight hours after infection, vector genome replication is determined by quantitative PCR (Q-PCR). A linear relationship between vector genome input and replicated copy number (slope = 2670 copies per vector genome) was determined, enabling detection of one infectious event per well by Q-PCR. The observed binomial distribution of the end-point data confirmed that single infectious events could be detected, and allowed calculation of infectious titers by the K?rber method. Analysis of an AAV2 reference vector, AAV-hFIX16, in 21 independent determinations gave an average ratio of AAV vector genomes (VG) to infectious units (IU) of 8.3 +/- 4.2 VG/IU, a value close to the theoretical limit. No significant differences in vector particle-to-infectious unit ratios were observed between vectors purified by column chromatography (9.3 +/- 5.0 VG/IU, n = 7) and cesium chloride gradient ultracentrifugation (6.4 +/- 3.2 VG/IU, n = 7).     

单克隆抗体与丝裂霉素交联物对人胃癌细胞的选择性杀伤作用

本文选用抗胃癌单克隆抗体(MoAb)3H 11与Mitomycin C(MMC)制备交联物。体外实验结果表明,3H 11-MMC对人胃癌细胞BGC 823有明显的杀伤作用。而且有明显的选择性:3H 11-MMC(相当于MMC 100 ng/ml)对靶细胞的杀伤率为71%,而对非靶细胞MCF-7仅为14%。MoAb 3H11与靶细胞预温后可使杀伤率(1 μg/ml)由85%下降为38%,而与MoAb 3G9预温却无明显影响。体内实验表明。3 H 11-MMC处理组,肿瘤形成的时间较各对照组明显延长,肿瘤生长速度明显减慢,具有显著性差异。     

The pharmacokinetics and pharmacodynamics of prasugrel in healthy Chinese, Japanese, and Korean subjects compared with healthy Caucasian subjects

Purpose

Prasugrel is a novel thienopyridine prodrug metabolised to an active metabolite that binds irreversibly to the platelet P2Y₁₂ receptor and inhibits adenosine diphosphate (ADP)-induced platelet aggregation. We compared prasugrel pharmacokinetics, pharmacodynamics, and tolerability in healthy Chinese, Japanese, Korean and Caucasian subjects.

Methods

In an open-label, single-centre, parallel-design study, 89 healthy subjects (25 Chinese, 20 Japanese, 22 Korean and 22 Caucasian) aged 20–65 years were given a prasugrel 60-mg loading dose (LD) followed by daily 10-mg maintenance doses (MD) for 7 days and then 5-mg MD for 10 days. Plasma concentrations of prasugrel’s active metabolite and inhibition of ADP-induced platelet aggregation (IPA) were determined.

Results

Mean exposure to prasugrel’s active metabolite in all treatment regimens was higher in each of the Asian groups than in the Caucasian group, although there was considerable overlap between individual exposure estimates in Asians and Caucasians. The mean IPA was also higher in Asians than in Caucasians following a prasugrel 60-mg LD, although the difference did not consistently achieve statistical significance. Prasugrel 10-mg or 5-mg MD produced statistically significantly higher IPA in each Asian group compared with that in the Caucasians. Prasugrel was well tolerated during the LD and MD regimens by all groups.

Conclusions

Mean exposure to the prasugrel active metabolite following prasugrel 60-mg LD and during daily 10-mg or 5-mg MD was higher in each of the Asian groups than in the Caucasian group, which resulted in greater platelet inhibition.