From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

     

Crack cocaine and sex

The impact of crack cocaine use on number of sex partners was examined using bivariate analyses and a logistic model on a national treatment cohort of 4939 individuals. Number of sex partners over the last 12 months was dichotomized as none/one versus multiple partners for the logistic analyses. The model included 11 independent variables not including prostitution or use of crack cocaine. For both genders, the bivariate analyses showed significant positive associations between crack use and number of partners regardless of type of sexual activity; those who used crack had more partners for all sexual activities queried, compared to those who did not. Cocaine, whether in powder or crack form, was positively associated with prostitution for both genders. For men the odds ratio for crack cocaine use ranged from 1.6 (heterosexual anal) to 5.5 (homosexual anal) and for women from 2.9 (heterosexual oral) to 4.1 (homosexual oral). If prostitution is added to the model the odds ratios are reduced for homosexual activities for men and reduced dramatically for all types of sexual activity for women.     

Tick bite protection with permethrin-treated summer-weight clothing

The number of tick bites received by individuals wearing either permethrin-treated or untreated summer clothing (T-shirt, shorts, socks, and sneakers) was compared during a controlled indoor study. Pathogen-free nymphal Ixodes scapularis Say were placed on the left shoe, right leg, and left arm of 15 (5/treatment group/d) human volunteers wearing untreated outfits or outfits treated with permethrin either commercially or using a do-at-home treatment kit. The number and location of ticks attached to subjects' skin were recorded 2.5 h postinfestation. Subjects wearing outfits treated with permethrin received 3.36 times fewer tick bites than subjects wearing untreated outfits. No statistically significant differences in number of tick bites were detected between commercial permethrin treatment (19.33%) and the do-at-home permethrin application method (24.67%). The success of permethrin-treated clothing in reducing tick bites varied depending on the specific article of clothing. Subjects wearing permethrin-treated sneakers and socks were 73.6 times less likely to have a tick bite than subjects wearing untreated footware. Subjects wearing permethrin-treated shorts and T-shirts were 4.74 and 2.17 times, respectively, less likely to receive a tick bite in areas related to those specific garments than subjects wearing untreated shorts and T-shirts. Ticks attached to subjects were classified as alive or dead before removal. On subjects wearing untreated outfits, 97.6% of attached nymphs were alive, whereas significantly fewer (22.6%) attached nymphs were alive on subjects wearing repellent-treated outfits. Results of this study demonstrate the potential of permethrin-treated summer clothing for significantly reducing tick bites and tick-borne pathogen transmission.     

Affective disorders and Health-Related Quality of Life (HRQoL) in adolescents and young adults with Multiple Sclerosis (MS): the moderating role of resilience

Purpose

To investigate the moderating role of resilience in the relationship between affective disorders and Health-Related Quality of Life (HRQoL) for adolescents and young adults with multiple sclerosis (MS).

Methods

A quantitative methodology was adopted. Fifty-three adolescents and young adults were interviewed to assess resilience as a personality trait (Ego-Resiliency Scale) and resilience as an interactive competence (CYRM-28), Health-Related Quality of Life (PedsQL 4.0), depression and anxiety (BDI-II and STAI-Y).

Results

Affective disorders, both depression (β = ?.38, p < .001) and anxiety (State β = –.35, p < .001; Trait β = ?.41, p < .001), were negatively associated with HRQoL. Data also showed that the resilience competencies using Individual (β = .22, p < .001) and relational resources (β = .12, p < .05) are significantly associated HRQoL. According to the regression analyses, we tested the moderating role of resilience competence using individual resources on the relationship between the Depression Cognitive Factor and Emotional Functioning. Data show that in step 2 of the regression analysis, we obtained a variation of β = ?.45 (p < .001) to β = ?.30 (p < .001) in the dimension for the Depression Cognitive Factor. The Sobel test showed that the moderating effect of resilience was significant regarding the increase in R² (p < .01).

Conclusions

Resilience competence using individual resources moderates the relationship between the Depression Cognitive Factor and Emotional Functioning in adolescents with MS. Our study suggests that to improve well-being for adolescents with MS resilience could play a key role.

     

In Vivo Imaging of Lymph Node Migration of MNP- and 111In-Labeled Dendritic Cells in a Transgenic Mouse Model of Breast Cancer (MMTV-Ras)

Purpose

The authors present a protocol for the in vivo evaluation, using different imaging techniques, of lymph node (LN) homing of tumor-specific dendritic cells (DCs) in a murine breast cancer model.

Procedures

Bone marrow DCs were labeled with paramagnetic nanoparticles (MNPs) or ¹¹¹In-oxine. Antigen loading was performed using tumor lysate. Mature DCs were injected into the footpads of transgenic tumor-bearing mice (MMTV-Ras) and DC migration was tracked by magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). Ex vivo analyses were performed to validate the imaging data.

Results

DC labeling, both with MNPs and with ¹¹¹In-oxine, did not affect DC phenotype or functionality. MRI and SPECT allowed the detection of iron and ¹¹¹In in both axillary and popliteal LNs. Immunohistochemistry and ??-counting revealed the presence of DCs in LNs.

Conclusions

MRI and SPECT imaging, by allowing in vivo dynamic monitoring of DC migration, could further the development and optimization of efficient anti-cancer vaccines.     

The direct mapping of the uptake of platinum anticancer agents in individual human ovarian adenocarcinoma cells using a hard X-ray microprobe

Uptake of platinum-based anticancer compounds into individual human ovarian andenocarcinoma cells was measured using an X-ray microprobe. The uptake of cisplatin, a platinum-based compound, in drug-resistant cells is decreased by approximately 50% after 24 h, compared with the uptake of the drug in nonresistant cells over the same time period. The Pt103 derivative of the drug, in contrast, showed an increased uptake by an order of magnitude in resistant cells over the same time period. Increased uptake appears to allow Pt103 to overcome the resistance mechanism developed by the cell. This work additionally shows that the X-ray microprobe is able to directly quantify Pt drug uptake on a subcellular level and can measure the mass of Pt down to a detectable limit of 20 attograms of Pt (2 x 10(-17) grams or 6 x 10(4) Pt atoms) in 1 s. Such exquisite elemental sensitivity combined with high spatial resolution paves the way for quantitative submicron three-dimensional mapping of elemental distributions within individual cells.     

Activity and DNA binding of new organoamidoplatinum (II) complexes

Two series of organoamidoplatinum (II) complexes were synthesized [Class 1, Pt(NRCH₂)₂L₂ and Class 2, Pt(NRCH₂CH₂NR₂)L(X)] and their antitumour activity examined by a range of in vitro, cellular and animal studies. All Class 1 compounds exhibited activity comparable to cisplatin in mouse leukemia L1210 cells, but were at least 8-fold more active against the cisplatin-resistant L1210/R line. The lead compound 1a (R=p–HC₆F₄) caused nearly complete tumour regression in the ADJ/PC6 mouse tumour model. Compound 1a exhibited similar DNA reactivity to cisplatin, resulting in virtually identical DNA sequence specificity as cisplatin, and had similar time and concentration dependency of interstrand crosslinks. Compared with cisplatin, 1a showed 3-fold greater cellular uptake into human ovarian carcinoma 2008 cells, and this was dramatically enhanced to 17-fold in the cisplatin-resistant 2008/R line. The activity of 1a, therefore, appears to be due at least in part to a greater cellular uptake into tumour cells, particularly cisplatin-resistant cells, and once in the cell it reacts with DNA in a similar manner to that of cisplatin. The enhanced uptake and enhanced cytotoxicity of Class 1 compounds, and 1a in particular, may be due to a greater hydrophobicity compared with cisplatin. The activity of the Class 2 compounds, especially in the cisplatin-resistant cell lines, is unusual because they have trans amine ligands, and further study of both classes of compounds is warranted.