Capecitabine-associated loss of fingerprints: A case report of a 62-year-old man with colorectal cancer suffering from capecitabine-induced adermatoglyphia

Background: Capecitabine is a prodrug of 5-fluorouracil (5-FU) and is converted to 5-FU in tumor tissue. Its primary mechanism of action is the suppression of DNA synthesis via inhibition of thymidylate synthetase. It is mostly used for neoadjuvant chemoradiation, adjuvant chemotherapy for colorectal cancer, metastatic breast, and localized and metastatic gastric cancer, among others. Adverse effects of capecitabine include diarrhea, hand-foot syndrome (HFS), pancytopenia, stomatitis, increased bilirubin, nausea, vomiting, and very rarely adermatoglyphia. Dermatoglyphics refers to fingerprints. Adermatoglyphia refers to the loss of fingerprints.Case review summary: We report the case of a 62-year-old male patient known case of locally advanced colorectal cancer. He presented in the clinic with residual disease after initially being treated with local surgery and chemoradiation with 5-FU. Positron emission tomography (PET) scan done at the time of presentation showed locally advanced disease. He was managed with surgery followed by chemotherapy with oxaliplatin 130 mg/m2 and capecitabine (Xeloda) 1500 mg twice a day for two weeks via three weekly cycles. Post cycle five, the patient complained of grade I HFS symptoms and inability to open a bank account due to loss of fingerprints. The patient was oblivious about this condition before that. After completing his adjuvant treatment that is six cycles of oxaliplatin and Xeloda, his symptoms of the HFS and loss of fingerprints, improved.Conclusion: As this case describes, adermatoglypia is a rare but noticeably side effect of capecitabine with a high chance of reversibility. Similar case reports have been reported with some normalization of fingerprints, after stopping treatment. Fingerprints have been used for centuries as means of identification in banks, aviation, immigration, computers, and mobile phones, amongst others. Awareness regarding the loss of fingerprints due to capecitabine is important for the patient and clinician, and alternative means of identification or other adaptive methods of recognition should be used for these patients

Effects of Dibutyryl Cyclic-AMP on Survival and Neuronal Differentiation of Neural Stem/Progenitor Cells Transplanted into Spinal Cord Injured Rats

Neural stem/progenitor cells (NSPCs) have great potential as a cell replacement therapy for spinal cord injury. However, poor control over transplant cell differentiation and survival remain major obstacles. In this study, we asked whether dibutyryl cyclic-AMP (dbcAMP), which was shown to induce up to 85% in vitro differentiation of NSPCs into neurons would enhance survival of transplanted NSPCs through prolonged exposure either in vitro or in vivo through the controlled release of dbcAMP encapsulated within poly(lactic-co-glycolic acid) (PLGA) microspheres and embedded within chitosan guidance channels. NSPCs, seeded in fibrin scaffolds within the channels, differentiated in vitro to betaIII-tubulin positive neurons by immunostaining and mRNA expression, in response to dbcAMP released from PLGA microspheres. After transplantation in spinal cord injured rats, the survival and differentiation of NSPCs was evaluated. Untreated NSPCs, NSPCs transplanted with dbcAMP-releasing microspheres, and NSPCs pre-differentiated with dbcAMP for 4 days in vitro were transplanted after rat spinal cord transection and assessed 2 and 6 weeks later. Interestingly, NSPC survival was highest in the dbcAMP pre-treated group, having approximately 80% survival at both time points, which is remarkable given that stem cell transplantation often results in less than 1% survival at similar times. Importantly, dbcAMP pre-treatment also resulted in the greatest number of in vivo NSPCs differentiated into neurons (37±4%), followed by dbcAMP-microsphere treated NSPCs (27±14%) and untreated NSPCs (15±7%). The reverse trend was observed for NSPC-derived oligodendrocytes and astrocytes, with these populations being highest in untreated NSPCs. This combination strategy of stem cell-loaded chitosan channels implanted in a fully transected spinal cord resulted in extensive axonal regeneration into the injury site, with improved functional recovery after 6 weeks in animals implanted with pre-differentiated stem cells in chitosan channels

Neural Stem/Progenitor Cells from the Adult Human Spinal Cord Are Multipotent and Self-Renewing and Differentiate after Transplantation

Neural stem/progenitor cell (NSPC) transplantation is a promising therapy for spinal cord injury (SCI). However, little is known about NSPC from the adult human spinal cord as a donor source. We demonstrate for the first time that multipotent and self-renewing NSPC can be cultured, passaged and transplanted from the adult human spinal cord of organ transplant donors. Adult human spinal cord NSPC require an adherent substrate for selection and expansion in EGF (epidermal growth factor) and FGF2 (fibroblast growth factor) enriched medium. NSPC as an adherent monolayer can be passaged for at least 9 months and form neurospheres when plated in suspension culture. In EGF/FGF2 culture, NSPC proliferate and primarily express nestin and Sox2, and low levels of markers for differentiating cells. Leukemia inhibitory factor (LIF) promotes NSPC proliferation and significantly enhances GFAP expression in hypoxia. In differentiating conditions in the presence of serum, these NSPC show multipotentiality, expressing markers of neurons, astrocytes, and oligodendrocytes. Dibutyryl cyclic AMP (dbcAMP) significantly enhances neuronal differentiation. We transplanted the multipotent NSPC into SCI rats and show that the xenografts survive, are post-mitotic, and retain the capacity to differentiate into neurons and glia

Bioengineering Neural Stem/Progenitor Cell-Coated Tubes for Spinal Cord Injury Repair

Cognizant Communication Corporation is the publisher and copyright holder of this article.The aim of this study was to understand the survival and differentiation of neural stem/progenitor cells (NSPCs) cultured on chitosan matrices in vivo in a complete transection model of spinal cord injury. NSPCs were isolated from the subependyma of lateral ventricles of adult GFP transgenic rat forebrains. The GFP-positive neurospheres were seeded onto the inner lumen of chitosan tubes to generate multicellular sheets ex vivo. These bioengineered neurosphere tubes were implanted into a completely transected spinal cord and assessed after 5 weeks for survival and differentiation. The in vivo study showed excellent survival of NSPCs, as well as differentiation into astrocytes and oligodendrocytes. Importantly, host neurons were identified in the tissue bridge that formed within the chitosan tubes and bridged the transected cord stumps. The excellent in vivo survival of the NSPCs coupled with their differentiation and maintenance of host neurons in the regenerated tissue bridge demonstrates the promise of the chitosan tubes for stem cell delivery and tissue regeneration

The regenerated bridge tissue contains host axons, blood vessels, and fibroblasts.

<p><b>A</b>) Representative image of endogenous axonal regeneration into the tissue bridge based on betaIII tubulin staining. <b>B</b>) Evidence of association between betaIII-positive endogenous axons with surviving GFP-positive NSPCs at six weeks. Synaptophysin staining is observed at the interface (inset). <b>C</b>) RECA1 staining for endothelial cells show blood vessel formation throughout the tissue bridge at 2 weeks. <b>D</b>) Prolyl-4-hydroxylase (rPH) staining of bridge tissue indicates that the majority of cells are collagen producing fibroblasts.</p

Differentiation profiles of NSPCs are impacted by dbcAMP treatment.

<p><b>A–L</b>) Representative images of tissue samples demonstrating NSPC differentiation profile of (A–C) nestin-positive progenitor cells, (D–F) BetaIII-positive neurons, (G–H) CC1-positive oligodendrocytes, and (J–L) GFAP-positive astrocytes. Scale bar represents 50 µm. <b>M</b>) Quantification of NSPC differentiation profile for the various treatment groups. Mean ± standard deviation are plotted, n = 3 to 5; significant differences noted with an asterisks, p<0.05. <b>N</b>) Deconvoluted confocal image of betaIII-positive NSPC-derived neurons (arrows) 6 weeks post-transplantation. Scale bar represents 50 µm.</p

Channel implantation after spinal cord transection facilitates tissue bridging, NSPC survival, and behavioural improvement over time.

<p><b>A</b>) Photograph of the surgical implantation of fibrin-filled chitosan channels. <b>B</b>) Tissue bridges obtained from animals 2 weeks after implantation. <b>C,D</b>) Longitudinal section of tissue bridge demonstrating NSPC survival after 6 weeks in an animal receiving dbcAMP pre-treatment (dbcAMP, 4div). Boxed area in (C) is magnified in (D). <b>E</b>) NSPC survival after 2 and 6 weeks for various treatment groups. <b>F</b>) Assessment of functional recovery using the BBB locomotor scale. After 6 weeks, rats receiving transplants of dbcAMP-pre-treated NSPCs show a statistically significant increase in hindlimb function relative to untreated animals (*, p<0.05). Mean ± standard deviation shown for n = 4 to 6.</p

NSPCs respond to dbcAMP <i>in vitro</i>.

<p><b>A</b>) Dose response curve of dbcAMP on neuronal differentiation of NSPCs after 7 days in culture. <b>B</b>) Differentiation profile of NSPCs after 7 days. NSPCs were treated with media containing 1 mM dbcAMP for 0, 1 or 7 days. Only sustained exposure to dbcAMP resulted in increased number of BetaIII-positive neurons. <b>C–J</b>) Representative images of NSPCs after 7 days in culture for markers of progenitors cells (nestin), neurons (BetaIII), oligodendrocytes (RIP), and astrocytes (GFAP). Scale bar represents 100 µm. <b>K</b>) Cell numbers at 1, 3, and 7 days in culture with or without 1 mM dbcAMP. <b>L</b>) Ki67 staining for proliferating cells after 3 days. <b>M</b>) Cell differentiation over time with or without 1 mM dbcAMP treatment. Data represented as mean ± standard (n = 3 to 9). Statistical differences denoted by *, p<0.05.</p

Microsphere-loaded channels effectively release dbcAMP <i>in vitro</i>.

<p><b>A</b>) Cumulative release profiles of dbcAMP from free-floating microspheres and microsphere-loaded channels. The process of embedding microspheres into channel walls is likely responsible for early degradation of PLGA and faster drug release from channels. <b>B</b>) Schematic of the entubulation strategy. NSPCs are seeded on fibrin scaffold within a chitosan channel. Drug-loaded PLGA microspheres release the differentiation factor dibutyryl cyclic-AMP in a local and sustained manner, influencing NSPCs to preferentially differentiate into neurons. <b>C</b>) Viability of NSPCs in a three-dimensional fibrin scaffold. Simultaneous staining of CalceinAM (green) and Ethidium homodimer (red) for live and dead cells respectively show good cell viability of NSPCs in fibrin scaffolds at 1 week. Scale bar represents 100 µm. <b>D–G</b>) Immunostaining of NSPCs for DAPI-nuclear stain and betaIII-tubulin with various dbcAMP treatments. Scale bar represents 100 µm. <b>H</b>) Quantification of betaIII-tubulin immunostained NSPCs with various dbcAMP treatments. <b>I,J</b>) Quantitative RT-PCR data for (I) betaIII tubulin and (J) nestin mRNA expression with various dbcAMP treatments, normalized to housekeeping gene HPRT. Data represented as mean ± standard (n = 3 to 6). Statistical differences denoted by *, p<0.05.</p

<i>In vivo</i> treatment groups.

<p><i>In vivo</i> treatment groups.</p