Modeling interactions between Human Equilibrative Nucleoside Transporter-1 and other factors involved in the response to gemcitabine treatment to predict clinical outcomes in pancreatic ductal adenocarcinoma patients.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by largely unsatisfactory responses to the currently available therapeutic strategies. In this study we evaluated the expression of genes involved in gemcitabine uptake in a selected cohort of patients with PDAC, with well-defined clinical-pathological features. METHODS: mRNA levels of hENT1, CHOP, MRP1 and DCK were evaluated by means of qRT-PCR in matched pairs of tumor and adjacent normal tissue samples collected from PDAC patients treated with gemcitabine after surgical tumor resection. To detect possible interaction between gene expression levels and to identify subgroups of patients at different mortality/progression risk, the RECursive Partitioning and Amalgamation (RECPAM) method was used. RESULTS: RECPAM analysis showed that DCK and CHOP were most relevant variables for the identification of patients with different mortality risk, while hENT1 and CHOP were able to identify subgroups of patients with different disease progression risk. CONCLUSION: hENT1, CHOP, MRP1 and DCK appear correlated to PDAC, and this interaction might influence disease behavior.

Case Report: Abdominal surgery with the support of Impella (SURGELLA), a new frontier to be explored.

A 74-year-old man with advanced heart failure was admitted to the hospital with a diagnosis of colorectal cancer, and he underwent surgery. To maintain stable hemodynamics, the Impella CP device was used. The patient was weaned from the device shortly after surgery, and he had an uneventful postoperative course. This case may pave the way for non-procrastinating surgery in patients with poorly stable hemodynamics.

Expression of the antiapoptotic protein BAG3 is a feature of pancreatic adenocarcinoma and its overexpression is associated with poorer survival.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers, being the fourth leading cause of cancer-related deaths. Long-term survival reaching 15% is achieved in less than 5% of patients who undergo surgery, and median survival is only 6 months in those with inoperable lesions. A deeper understanding of PDAC biologic characteristics as well as novel prognostic markers are therefore required to improve outcomes. Herein we report that BAG3, a protein with recognized anti-apoptotic activity, was expressed in 346 PDACs analyzed, but was not expressed in the surrounding nonneoplastic tissue. In a cohort of 66 patients who underwent radical resection (R0), survival was significantly shorter in patients with high BAG3 expression (median, 12 months) than in those with low BAG3 expression (median, 23 months) (P = 0.001). Furthermore, we report that BAG3 expression in PDAC-derived cell lines protects from apoptosis and confers resistance to gemcitabine, offering a partial explanation for the survival data. Our results indicate that BAG3 has a relevant role in PDAC biology, and suggest that BAG3 expression level might be a potential marker for prediction of patient outcome.

High Blood Concentration of Leukocyte-Derived Extracellular Vesicles Is Predictive of Favorable Clinical Outcomes in Patients with Pancreatic Cancer: Results from a Multicenter Prospective Study.

Pancreatic cancer (PC) is one of the leading causes of cancer-related death worldwide. Identification of novel tumor biomarkers is highly advocated in PC to optimize personalized treatment algorithms. Blood-circulating extracellular vesicles hold promise for liquid biopsy application in cancer. We used an optimized flow cytometry protocol to study leukocyte-derived EVs (CD45+) and PD-L1+ EVs in blood from 56 pancreatic cancer patients and 48 healthy controls (HCs). Our results show that PC patients presented higher blood levels of total EVs (p = 0.0003), leukocyte-derived EVs (LEVs) (p = 0.001) and PD-L1+ EVs (p = 0.01), as compared with HCs. Interestingly, a blood concentration of LEVs at baseline was independently associated with improved overall survival in patients with borderline resectable or primary unresectable PC (HR = 0.17; 95% CI 0.04-0.79; p = 0.02). Additionally, increased blood-based LEVs were independently correlated with prolonged progression-free survival (HR = 0.10; 95% CI 0.01-0.82; p = 0.03) and significantly associated with higher disease control rate (p = 0.02) in patients with advanced PC receiving standard chemotherapy. Notably, a strong correlation between a decrease in blood LEVs concentration during chemotherapy and disease control was observed (p = 0.005). These intriguing findings point to the potential of LEVs as novel blood-based EV biomarkers for improved personalized medicine in patients affected by PC.

The Complex Network between Inflammation and Colorectal Cancer: A Systematic Review of the Literature.

BACKGROUND: colorectal cancer (CRC) has a multifactorial etiology which comprises microbiota, genetic predisposition, diet, environmental factors, and last but not least, a substantial contribution by inflammation. The aim of this study is to conduct a systematic review of the literature regarding the strong link between inflammation and colorectal cancer. METHODS: A systematic review of the literature on PubMed (Medline), Scopus, Cochrane and EMBase databases was performed, following the PRISMA 2020 guidelines. Each paper was reviewed by two groups of researchers in a single-blind format by using a pre-planned Microsoft© Excel® grid. RESULTS: Using automated research filters, 14,566 studies were included, but 1% was found significant by the reviewers. Seventy pathways of inflammation were described in the sequence of inflammation-carcinogenesis, and anti-tumorigenic molecules were also found. CONCLUSION: several studies suggest a strong role of inflammation in the tumorigenesis of colorectal cancer through different pathways: this may have a diagnostic and clinical role and also therapeutic purpose in preventing carcinogenesis by treating inflammation. In vitro tests support this theory, even if many other clinical trials are necessary. The present paper was registered in the OpenScience Framework registry (Identifier: DOI 10.17605/OSF.IO/2KG7T).

Outcome after single-site robotic cholecystectomy: An initial single center's experience.

BACKGROUND: Although laparoscopic cholecystectomy (LC) is the gold standard for symptomatic gallbladder disease, a single-incision approach may be a new challenge in order to achieve minimization of surgical trauma. Single-site robotic cholecystectomy (SSRC) is able to offset the ergonomic limitation of laparoscopic single-site cholecystectomy and improves cosmesis. METHODS: We present a single-institution initial experience of SSRC for cholecystolithiasis. Intra-operative and post-operative data of patients were reviewed to assess the technical feasibility and cosmetic outcome. RESULTS: We evaluated a series of 27 consecutive patients retrospectively analyzed and prospectively collected who underwent SSRC. One patient was excluded from the final analysis because they converted to open procedure. The female/male ratio was 17/9, with mean age of 48 ± 12 years. The body mass index mean value was 26.0 ± 4.2. The mean operative time was 99.6 ± 21.5 minutes. No intra- or post-operative complications and readmissions were recorded. At 12 months follow up, every patient received the Body Image Questionnaire (BIQ) and a Photo Series Questionnaire. We recorded three patients (11.5%) with post-operative incisional hernia. Scores of the BIQ subscale for body image perception were 6 ± 1.2, while the scores of scar cosmesis were 21.1 ± 3.0. A statistically significant improvement in scar self-rating from T0 to T1 (P < .01) was found. CONCLUSION: In our initial experience SSRC may be preferred to treat patients with higher needs in terms of cosmesis and body image perception. Lower costs for rent, maintenance and consumables may allow the spread of robotic surgery also for singe site cholecystectomy.

Transduodenal surgical ampullectomy: a procedure that requires a multidisciplinary approach.

Trans-duodenal surgical ampullectomy (TSA) was first described in 1899. Nowadays its role in ampullary tumor surgery is still a matter of debate and requires a multidisciplinary approach. The aim of this study is to evaluate the results of TSA as a curative treatment for benign and selected malignant tumors arising from the ampulla in a single-institution experience. Sixteen patients with periampullary tumors that underwent TSA in our surgical units between January 2012 and January 2017 were included in the study. Patient demographic characteristics, pre or postoperative endoscopic interventions, operative procedures, postoperative morbidity and mortality, hospitalization, follow-up time, and quality of life questionnaire were analyzed. Mean operative time was 238.5 min (range 180-390), mean tumor size was 2.3 cm (range 1.5-3.9). The microscopic surgical outcome was R0 for 14 patients. The most frequent findings in terms of histological type were high-grade dysplasia/pTis (43.7%), low-grade dysplasia in 37.5% patients, invasive adenocarcinoma in 2 cases (12.5%), chronic inflammation in 1 case (6.3%). The readmission rate was 18.8% (3/16) and in 2 cases (12.5%) relaparotomy was required. The cumulative median duration of follow-up was 50 months (range 1-96). 90-days mortality was 6.2%. Mean hospital stay was 12 days (range 8-60). Our results confirm that TSA offers good results in terms of morbidity and mortality; still, it remains a challenging procedure that requires particular surgical experience and operative skills. A pre-operative planning in a multidisciplinary board should be carried out prior to the procedure.

Laparoscopic Versus Open Hartmann Reversal: A Case-Control Study.

BACKGROUND: Laparoscopic reversal of Hartmann's procedure (LHR) offers reduced morbidity compared with open Hartmann's reversal (OHR). The aim of this study is to compare the outcome of laparoscopic versus open Hartmann reversal. MATERIALS AND METHODS: Thirty-four patients who underwent Hartmann reversal between January 2017 and July 2019 were evaluated. Patients underwent either LHR (n = 17) or OHR (n = 17). Variables such as numbers of patients, patient's age, sex, body mass index (BMI), comorbidities, ASA (American Society of Anesthesiology) score, indication for previous open sigmoid resection, mean operation time, rate of conversion to open surgery, length of hospital stay, mortality, and morbidity were retrospectively evaluated. RESULTS: The two groups of patients were homogeneous for gender, age, body mass index, cause of primary surgery, time to reversal, and comorbidities. In 97% of the cases, HP was done by open surgery. Our data revealed no difference in mean operation time (LHR: 180.5 ± 35.1 vs. OHR: 225.2 ± 48.4) and morbidity rate, although, in OHR group, there were more severe complications. Less intraoperative blood loss (LHR: 100 ± 40 mL vs. OHR: 450 ± 125 mL; p value <0.001), shorter time to flatus (LHR: 2.4 days vs. OHR: 3.6 days; p value <0.021), and shorter hospitalization (LHR: 4.4 vs. OHR: 11.2 days; p value <0.001) were observed in the LHR group. Mortality rate was null in both groups. Discussion. LHR is feasible and safe even for patients who received a primary open Hartmann's procedure. We suggest careful patient's selection allowing LHR procedures to highly skilled laparoscopy surgeons.

MicroRNA co-expression networks exhibit increased complexity in pancreatic ductal compared to Vater's papilla adenocarcinoma.

MiRNA expression abnormalities in adenocarcinoma arising from pancreatic ductal system (PDAC) and Vater's papilla (PVAC) could be associated with distinctive pathologic features and clinical cancer behaviours. Our previous miRNA expression profiling data on PDAC (n=9) and PVAC (n=4) were revaluated to define differences/similarities in miRNA expression patterns. Afterwards, in order to uncover target genes and core signalling pathways regulated by specific miRNAs in these two tumour entities, miRNA interaction networks were wired for each tumour entity, and experimentally validated target genes underwent pathways enrichment analysis. One hundred and one miRNAs were altered, mainly over-expressed, in PDAC samples. Twenty-six miRNAs were deregulated in PVAC samples, where more miRNAs were down-expressed in tumours compared to normal tissues. Four miRNAs were significantly altered in both subgroups of patients, while 27 miRNAs were differentially expressed between PDAC and PVAC. Although miRNA interaction networks were more complex and dense in PDAC than in PVAC, pathways enrichment analysis uncovered a functional overlapping between PDAC and PVAC. However, shared signalling events were influenced by different miRNA and/or genes in the two tumour entities. Overall, specific miRNA expression patterns were involved in the regulation of a limited core signalling pathways in the biology landscape of PDAC and PVAC.

Human inflammatory bowel disease does not associate with Lawsonia intracellularis infection.

BACKGROUND: There is increasing evidence that bacterial infection of the intestinal mucosa may contribute to the pathogenesis of inflammatory bowel diseases (IBD). In pigs, an obligate intracellular bacterium, Lawsonia intracellularis (LI), was shown to cause proliferative enteropathy (PE) of which some forms display histological and clinical similarities to human IBD. Since LI-similar Desulfovibrio spp. may infect human cells, we hypothesized that LI might be associated with the development of human IBD. RESULTS: In human intestinal tissue samples, PCR using LLG, 50SL27, LSA and strictly LI-specific 16SII primers, yielded either no amplicons or products with weak homology to human genomic sequences. Sequencing of these amplicons revealed no specificity for LI. However, amplification of DNA with less specific 16SI primers resulted in products bearing homology to certain Streptococcus species. These 16SI-amplified products were present in healthy and diseased specimens, without obvious prevalence. CONCLUSION: LI is not associated with the pathogenesis of UC or CD. Whether an immunologic response to commensal bacteria such as streptococci may contribute to the chronic inflammatory condition in IBD, remained to be determined.

Support Vector Machine Based on microRNA Expression Profiles to Predict Histological Origin of Ampullary Carcinoma: Case Report of a Patient Affected From Adenocarcinoma of the Papilla of Vater With Lynch Syndrome.

Adenocarcinomas of Vater's papilla (PVAC) may originate from either the pancreatic duct or the intestinal epithelium. Conflicting data have been reported about the frequency of the 2 anatomical entities and their influence on patients' prognosis. To ascertain the anatomical origin of PVAC in a family member of a Lynch syndrome kindred, we searched for microRNA (miRNA) expression profiles on resected tumor specimens. The support vector machine was trained on our previous miRNAs expression data sets of pancreatic and colorectal tissue samples and used to classify the site of origin of the tumor in our patient. The support vector machine worked by contrasting the profiles of miRNAs in patients with pancreatic ductal and colorectal cancers to that of our patient, which was finally classified as pancreatic ductal adenocarcinoma accordingly to alterations of 55 miRNAs. The PVAC might be originated from ductal epithelium rather than from the intestinal mucosa of the papilla in the case at issue. Alteration of miR-548b-3p, miR-551a, miR-21, miR-92a, miR-let-7i, and miR-181a* emerged as potentially associated with cancer genetic susceptibility in PVAC.

Overexpressed decorin in pancreatic cancer: potential tumor growth inhibition and attenuation of chemotherapeutic action.

PURPOSE: The aim of this study was to investigate the expression and significance of decorin in pancreatic cancer. EXPERIMENTAL DESIGN: Decorin expression in normal pancreas and excised tumors was examined by real-time quantitative PCR, Western blot analysis, and immunohistochemistry. Reverse transcription-PCR was used to analyze cultures of pancreatic cancer and stellate cells. Growth-inhibitory effects of decorin in vitro were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test, Western blot, and fluorescence-activated cell-sorting analysis. RESULTS: Pancreatic cancer was characterized by striking overexpression of decorin mRNA in tumor tissues (9-fold by real-time quantitative PCR; 44 patients versus 18 healthy donors; P < 0.01). Strong decorin immunostaining was observed in the extracellular matrix of pancreatic cancer tissue, whereas tumor cells were devoid of decorin. Double staining for anti-smooth muscle actin and decorin and reverse transcription-PCR analysis of primary cultures revealed pancreatic stellate cells as the putative source of decorin. Human recombinant decorin was able to suppress growth of pancreatic cancer cells in vitro through p21 mediated G(1)-S block of the cell cycle. However, in contrast to the previously described chemotherapy-potentiating capacity of decorin, this proteoglycan attenuated the cytostatic action of carboplatin and gemcitabine toward pancreatic cancer cells. CONCLUSIONS: Decorin might exert an antiproliferative effect toward pancreatic cancer cells, thus playing a role in a host stromal reaction aimed at sequestering and inhibiting growing malignant cells. However, in clinical settings, the importance of collagen-associated decorin as a moderate antitumor modality would be undermined by its ability to attenuate the efficiency of chemotherapeutics. Considering the general failure of adjuvant therapies in pancreatic cancer, the role of decorin in this process warrants further investigation.

SIRT1 and circadian gene expression in pancreatic ductal adenocarcinoma: Effect of starvation.

Pancreatic cancer (PC), the fourth leading cause of cancer-related deaths, is characterized by high aggressiveness and resistance to chemotherapy. Pancreatic carcinogenesis is kept going by derangement of essential cell processes, such as proliferation, apoptosis, metabolism and autophagy, characterized by rhythmic variations with 24-h periodicity driven by the biological clock. We assessed the expression of the circadian genes ARNLT, ARNLT2, CLOCK, PER1, PER2, PER3, CRY1, CRY2 and the starvation-activated histone/protein deacetylase SIRT1 in 34 matched tumor and non-tumor tissue specimens of PC patients, and evaluated in PC derived cell lines if the modulation of SIRT1 expression through starvation could influence the temporal pattern of expression of the circadian genes. We found a significant down-regulation of ARNLT (p = 0.015), CRY1 (p = 0.013), CRY2 (p = 0.001), PER1 (p < 0.0001), PER2 (p < 0.001), PER3 (p = 0.001) and SIRT1 (p = 0.017) in PC specimens. PER3 and CRY2 expression levels were lower in patients with jaundice at diagnosis ( < 0.05). Having adjusted for age, adjuvant therapy and tumor stage, we evidenced that patients with higher PER2 and lower SIRT1 expression levels showed lower mortality (p = 0.028). Levels and temporal patterns of expression of many circadian genes and SIRT1 significantly changed upon serum starvation in vitro, with differences among four different PC cell lines examined (BXPC3, CFPAC, MIA-PaCa-2 and PANC-1). Serum deprivation induced changes of the overall mean level of the wave and amplitude, lengthened or shortened the cycle time and phase-advanced or phase-delayed the rhythmic oscillation depending on the gene and the PC cell line examined. In conclusion, a severe deregulation of expression of SIRT1 and circadian genes was evidenced in the cancer specimens of PC patients, and starvation influenced gene expression in PC cell lines, suggesting that the altered interplay between SIRT1 and the core circadian proteins could represent a crucial player in the process of pancreatic carcinogenesis.

BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages.

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential.

Genetic variants of membrane metallopeptidase genes in inflammatory bowel diseases.

BACKGROUND: The substance P pathway modulates neuroimmune interactions during intestinal inflammation. AIMS: To analyse mucosal expression and genetic variants of the genes coding for substance P, neurokinin-1 receptor and neutral endopeptidase in patients with inflammatory bowel disease. METHODS: qRT-PCR was used to analyse mRNA levels in matched, paired samples of inflamed colonic mucosa and adjacent non-inflamed endoscopic tissue from 26 Crohn's disease and 25 ulcerative colitis patients. Allele and genotype frequencies of tag-SNPs were determined in 908 Crohn's disease, 929 ulcerative colitis, and 853 controls. Expression levels and genotype distributions were examined within patients' clinical sub-phenotypes. RESULTS: All 3 evaluated genes were overexpressed in inflamed tissues from Crohn's disease (P=0.033, P=4×10(-5), P=0.001), while in ulcerative colitis only higher levels of the gene coding for neutral endopeptidase were statistically significant (P=2.5×10(-5)). Smoking habit and perianal disease were significantly associated with substance P (P=0.002) and neurokinin-1 receptor levels (P=0.02) in Crohn's disease. Neutral endopeptidase rs701109 variant was associated with inflammatory bowel disease (Crohn's disease: P=0.022; ulcerative colitis: P=0.045), and with the need for colectomy in ulcerative colitis (P=0.008, OR=2.46, 95% CI=1.27-4.76). CONCLUSIONS: Genetic variants of the gene coding for neutral endopeptidase might affect the neuroimmune interaction during intestinal inflammation and influence clinical sub-phenotypes in patients with inflammatory bowel disease.

Correlations among PPARγ, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer.

Emerging evidence indicates that peroxisome proliferator-activated receptor γ (PPARγ) and DNA methyltransferases (DNMTs) play a role in carcinogenesis. In this study we aimed to evaluate the expression of PPARγ, DNMT1, and DNMT3B and their correlation with clinical-pathological features in patients with pancreatic cancer (PC), and to define the effect of PPARγ activation on DNMTs expression in PC cell lines. qRT-PCR analysis showed that DNMT3B expression was downregulated in tumors compared to normal tissues (P = 0.03), whereas PPARγ and DNMT1 levels did not show significant alterations in PC patients. Expression levels between PPARγ and DNMT1 and between DNMT1 and DNMT3B were highly correlated (P = 0.008 and P = 0.05 resp.). DNMT3B overexpression in tumor tissue was positively correlated with both lymph nodes spreading (P = 0.046) and resection margin status (P = 0.04), and a borderline association with perineural invasion (P = 0.06) was found. Furthermore, high levels of DNMT3B expression were significantly associated with a lower mortality in the whole population (HR = 0.485; 95%CI = 0.262-0.895, P = 0.02) and in the subgroup of patients without perineural invasion (HR = 0.314; 95%CI = 0.130-0.758; P = 0.01), while such association was not observed in patients with tumor invasion into perineural structures (P = 0.70). In conclusion, in vitro and in vivo PPARγ and DNMTs appear interrelated in PC, and this interaction might influence cell phenotype and disease behavior.

Time-Qualified Patterns of Variation of PPARγ, DNMT1, and DNMT3B Expression in Pancreatic Cancer Cell Lines.

Carcinogenesis is related to the loss of homeostatic control of cellular processes regulated by transcriptional circuits and epigenetic mechanisms. Among these, the activities of peroxisome proliferator-activated receptors (PPARs) and DNA methyltransferases (DNMTs) are crucial and intertwined. PPARγ is a key regulator of cell fate, linking nutrient sensing to transcription processes, and its expression oscillates with circadian rhythmicity. Aim of our study was to assess the periodicity of PPARγ and DNMTs in pancreatic cancer (PC). We investigated the time-related patterns of PPARG, DNMT1, and DNMT3B expression monitoring their mRNA levels by qRT-PCR at different time points over a 28-hour span in BxPC-3, CFPAC-1, PANC-1, and MIAPaCa-2 PC cells after synchronization with serum shock. PPARG and DNMT1 expression in PANC-1 cells and PPARG expression in MIAPaCa-2 cells were characterized by a 24 h period oscillation, and a borderline significant rhythm was observed for the PPARG, DNMT1, and DNMT3B expression profiles in the other cell lines. The time-qualified profiles of gene expression showed different shapes and phase relationships in the PC cell lines examined. In conclusion, PPARG and DNMTs expression is characterized by different time-qualified patterns in cell lines derived from human PC, and this heterogeneity could influence cell phenotype and human disease behaviour.

Increase in substance P precursor mRNA in noninflamed small-bowel sections in patients with Crohn's disease.

BACKGROUND: Neuropeptides, such as substance P (SP), are mediators of neurogenic inflammation and play an important role in inflammatory disorders. To further investigate the role of the SP pathway in inflammatory bowel disease (IBD), we analyzed the following in normal intestinal tissue specimens and in tissue specimens from patients with Crohn's disease (CD) and ulcerative colitis (UC): neurokinin receptor-1 (NK-1R); its isoforms (NK-1R-L and NK-1R-S); its ligand SP, encoded by preprotachykinin-A (PPT-A); and the SP-degradation enzyme, neutral endopeptidase (NEP). METHODS: Real-time quantitative reverse transcription-polymerase chain reaction was used to simultaneously determine the expression of NK-1R-L, NK-1R-S, and PPT-A. Protein levels of NK-1R and NEP were determined by immunoblot analysis. RESULTS: In noninflamed small-bowel tissue samples of CD patients, PPT-A mRNA expression was significantly increased, whereas there was no difference between inflamed or noninflamed UC and normal intestinal tissue samples. Examining subgroups of diverse intestinal segments from CD and UC samples with various levels of inflammation revealed no differences in NK-1R-L and NK-1R-S mRNA expression, whereas there was a tendency toward overall lower NK-1R-S mRNA copy numbers. Immunoblot analysis showed upregulation of NK-1R protein levels in cases of IBD, with more pronounced enhancement in cases of CD than in UC. For NEP, there were no differences in protein levels in normal, CD, and UC intestinal tissues. COMMENTS: These observations suggest a contribution of SP and its receptor, NK-1R, in the local inflammatory reaction in IBD and particularly in ileal CD. Moreover, significant upregulation of PPT-A mRNA in the noninflamed ileum of these patients suggests an influence of inflamed intestines on their healthy counterparts.