Unusual localizations of sentinel lymph nodes in early stage cervical cancer: a review

ObjectiveThe aim of this study was to systematically determine the frequency of unusual localizations of sentinel lymph node in patients with early stage cervical cancer.MethodsWe performed a comprehensive computer literature search of English and French language studies in human subjects on sentinel node procedures in PUBMED database up to December 2010. For each article two reviewers independently performed data extraction using a standard form to determine the route of unusual lymphatic spread of sentinel procedures in cervical cancer.ResultsAccording to our search, 83.7% of detected sentinel lymph nodes in patients with cervical cancer were in expected localizations (i.e., external iliac, obturator, internal iliac or interiliac). The unusual localizations were: 6.6% in the common iliac chain, 4.31% parametrial, 1.26% sacral, 2% in the lower para-aortic area and 0.07% in the inguinal chain.ConclusionThe unusual localizations of sentinel lymph nodes impose to the gynecologic surgeons to be able to perform lymph node dissection in all the territories potentially affected.     

TRP calcium channel and breast cancer: expression, role and correlation with clinical parameters

Breast cancer (BC) has the highest incidence rate in women in industrialized countries. Statistically, it is estimated that one out of 10 women will develop BC during her life. Evidence is accumulating for the role of ion channels in the development of cancer. Most studied ion channels in BC are K(+) channels, which are involved in cell proliferation, cell cycle progression and cell migration, and Na(+) channels, which correlate with invasiveness. Emerging studies demonstrated the role of Ca(2+) signaling in cancer cell proliferation, survival and migration. Recent findings demonstrated that the expression and/or activity of the transient receptor potential (TRP) channels are altered in several cancers. Among the TRP families, TRPC (canonical or classical), TRPM (melastatin) and TRPV (vanilloid) are related to malignant growth and cancer progression. Although these channels are frequently and abundantly expressed in many tumors, their specific expression, activity and roles in BC are still poorly understood. The expression of TRP channels has also been proposed as a tool for diagnosis, prognosis and/or therapeutic issues of several diseases. In cancer, TRPV6 and TRPM8 have been proposed as tumor progression markers of prostate cancer outcome and TRPC6 as a novel therapeutic target for esophageal carcinoma. Interestingly high levels of TRPC3 expression correlate with a favorable prognosis in patients with lung adenocarcinoma. Our team has recently reported the expression and role of TRPC1, TRPC6, TRPM7, TRPM8 and TRPV6 in BC cell lines and primary cultures. We have also investigated TRP expression and their clinical significance in human breast adenocarcinoma and we suggest that TRP channels are new potential BC markers. Indeed TRPC1 and TRPM8 may be considered as good prognosis markers of well-differentiated tumors, TRPM7 as a proliferative marker of poorly differentiated tumors and TRPV6 as a prognosis marker of aggressive cancers. In this review, we summarize the data reported to date regarding the changes in TRP expression associated with BC. We also discuss the importance of TRP channels in BC cells proliferation and migration and their interest as new BC markers.     

Exploration of the functional hierarchy of the basal layer of human epidermis at the single‐cell level using parallel clonal microcultures of keratinocytes

Please cite this paper as: Exploration of the functional hierarchy of the basal layer of human epidermis at the single‐cell level using parallel clonal microcultures of keratinocytes. Experimental Dermatology 2010. Abstract: The basal layer of human epidermis contains both stem cells and keratinocyte progenitors. Because of this cellular heterogeneity, the development of methods suitable for investigations at a clonal level is dramatically needed. Here, we describe a new method that allows multi‐parallel clonal cultures of basal keratinocytes. Immediately after extraction from tissue samples, cells are sorted by flow cytometry based on their high integrin‐α6 expression and plated individually in microculture wells. This automated cell deposition process enables large‐scale characterization of primary clonogenic capacities. The resulting clonal growth profile provided a precise assessment of basal keratinocyte hierarchy, as the size distribution of 14‐day‐old clones ranged from abortive to highly proliferative clones containing 1.7 × 10⁵ keratinocytes (17.4 cell doublings). Importantly, these 14‐day‐old primary clones could be used to generate three‐dimensional reconstructed epidermis with the progeny of a single cell. In long‐term cultures, a fraction of highly proliferative clones could sustain extensive expansion of >100 population doublings over 14 weeks and exhibited long‐term epidermis reconstruction potency, thus fulfilling candidate stem cell functional criteria. In summary, parallel clonal microcultures provide a relevant model for single‐cell studies on interfollicular keratinocytes, which could be also used in other epithelial models, including hair follicle and cornea. The data obtained using this system support the hierarchical model of basal keratinocyte organization in human interfollicular epidermis.     

Preventive and curative effect of Trigonella foenum-graecum L. seeds in C57BL/6J models of type 2 diabetes induced by high-fat diet

Ethnopharmacological relevance

Trigonella foenum-graecum L. (TFG) is traditionally used to treat diabetes in North Africa. we therefore tested the effects of the hydro-alcoholic extract of TFG seeds in a C57/BL6J mouse model of diabetes induced by a standardised high-fat diet (HFD).

Materials and methods

Plant extracts (2 g/kg daily) were administered orally by gavage at the start of HFD, or after confirmation of established diabetes (17th week), for 20 or 18 weeks, respectively, to male C57BL/6J mice. Animals were weighed; food intake and plasma glucose, lipid profile, insulin and insulin resistance were measured.

Results

TFG extracts opposed the development of diabetes: compared with untreated HFD mice, TFG-treated HFD mice had lower mean (±SD) plasma glucose (129.3±39.4 vs. 183.1±19.1 mg/dL, p<0.05), plasma insulin (1.3±0.8 vs. 3.1±1.8 ng/mL, p<0.05) and triglycerides (18.9±12.9 vs. 48.9±12.1 mg/dL, p<0.05), and less insulin resistance as estimated by the homeostasis model assessment (HOMA: 9.7±11.1 vs. 38.3±26.6, p<0.05). In mice with established diabetes, TFG reduced fasting plasma glucose (170.4±24.1 vs. 229.0±20.8 mg/dL, p<0.05), plasma insulin (1.7± 1.3 vs. 3.3±14.3 ng/mL, p<0.05) and insulin resistance (HOMA: TFG: 19.2±15.7 vs. HFD control: 38.5±30.3, p<0.05). In addition, administration of TFG extract also caused significant reduction in triglycerides (17.9±9.7 vs. 62.8±18.3 mg/dL, p<0.05) and total cholesterol (1.30±0.20 vs. 1.80±1.10 g/L, p<0.05), and an increase in HDL-cholesterol (1.6±0.2 vs. 1.2±0.1 g/L). The plant extract had no effect on calorie intake or body weight.

Conclusion

TFG extract opposed the development of experimental HFD diabetes in mice, and had an anti-diabetic effect in mice with established diabetes.     

Apparent virus contamination in biopharmaceutical product at centocor

Out-of-specification (OOS) results were reported by a contract lab in the in vitro adventitious agent assay (AVA) for two products manufactured using mouse myeloma cells in perfusion bioreactors. Cytopathic effect observed for test article-inoculated MRC-5 monolayers resembled foci seen in tissue culture cells infected with transforming viruses. All reasonable known technologies, including highly sensitive, state-of-the-art methodologies and multiple, redundant, and orthogonal methods, were deployed to screen broadly for potential viral and microbial contaminants. Due to the appearance of apparent foci, testing for murine, bovine, and human polyomavirus contamination was heavily represented in the analytical investigation. The results obtained in this extensive screening provided convincing evidence for the lack of an infectious viral or other biological agent. Although the initial investigation produced no reason to invalidate AVA yielding OOS results or to suspect an assay artifact, an extended evaluation revealed several irregularities at the contract test lab reporting the OOS results. The extended investigation also included attempts to reproduce OOS results at alternate contract testing labs and an inter-laboratory study in which methodological differences in the AVA at the three different contract labs were investigated. Only the contract lab initially reporting the OOS results reported foci during this extended evaluation. The results of the inter-laboratory study suggested that the foci artifact might be attributed to the prolonged exposure of the MRC-5 monolayer to cell debris present in the test article. Confocal immunofluorescence microscopy and transmission electron microscopy were subsequently used to provide convincing evidence that the foci observed in test article-inoculated AVA wells were composed of a core of degraded myeloma cell debris covered by one or more layers of MRC-5 cells. The observation that the foci were detected in the AVA at a contract lab where the MRC-5 monolayer is exposed to production cell line debris for a prolonged period strongly suggests that these foci form when MRC-5 grow over the cell debris present in the test article. The cumulative results of the investigation supported the conclusion that the OOS results were artifacts of the AVA test system and not a result of contamination with a virus or other biological agent. Testing was discontinued at the contract lab generating the OOS results and validated at a second contract lab. Manufacturing resumed in consultation with health authorities. The lots were retested following a standard operating procedure (SOP) already in place and ultimately dispositioned for use in normal distribution channels.     

Borderline personality organization and psychopathic traits in nonclinical adolescents: relationships of identity diffusion, primitive defense mechanisms and reality testing with callousness and impulsivity traits

Although psychotherapeutic observation and empirical data suggest a link between borderline and antisocial personality disorder or traits in adolescents, there is no study on the relationships of borderline personality organization (BPO) and psychopathic traits in adolescents. The aim of this study was to explore the relationship of structural criteria of (BPO) as assessed by the French version of the Borderline Personality Inventory (BPI), with psychopathic traits, as assessed by the French version of the Levenson Self-Report Psychopathy Scale (LSRP), in a nonclinical sample of 243 adolescents. Significant correlations were found between the BPI scales of identity diffusion, primitive defense mechanisms, impaired reality testing, and psychopathic traits of callousness and impulsivity, suggesting that BPO may contribute to psychopathic traits in nonforensic, nonclinical adolescents.