vasoactive-intestinal-peptide and Colorectal-Neoplasms

Radiolabelled vasoactive intestinal peptide (VIP) and its analogues have shown their potential as imaging agents for diagnosing tumours expressing VIP receptor. However, the fast proteolytic degradation in vivo has limited their clinical use.. To prepare the 18F-labelled (R8,15,21, L17)-VIP analogue in a convenient way and to evaluate its potential as an imaging agent for VIP receptor-positive tumours.. Radiolabelled (R8,15,21, L17)-VIP was obtained by conjugation with N-succinimidyl 4-([18F]fluoromethyl) benzoate and purified by HPLC. Radiochemical purity and specific radioactivity were measured by analytical HPLC. In-vitro stability of the product was carried out in HSA solution and analysed by HPLC. Biodistribution study was carried out in mice bearing C26 colorectal tumours.. 18F-(R8,15,21, L17)-VIP was obtained in greater than 99% radiochemical purity within 60 min in decay-for-corrected radiochemical yields of 21.8+/-4.7% (n=5) and a specific activity of 17.76 GBq x mumol(-1) at the end of synthesis (EOS). Results of in-vitro studies demonstrated a high stability in human serum albumin (HSA) solution. Biodistribution data showed a rapid blood clearance and specific binding towards receptor-positive tumours.. 18F-(R8,15,21, L17)-VIP was prepared by a convenient method. Preliminary biodistribution results showed its potential for imaging tumours over-expressing VIP receptors and encouraged further investigation.

Topics: Animals; Colorectal Neoplasms; Humans; Iodine Radioisotopes; Mice; Mice, Inbred BALB C; Radionuclide Imaging; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide

Intestinal adenocarcinomas and various endocrine tumors express large numbers of high-affinity receptors for vasoactive intestinal peptide (VIP). We have evaluated the usefulness of scanning with VIP labeled with iodine-123 for tumor localization in patients with gastrointestinal tumors.. Radioiodinated VIP was purified by high-pressure liquid chromatography and administered as a single intravenous bolus injection (300 pmol [1 microgram]). Scanning with radiolabeled VIP was compared with computed tomography and scanning with somatostatin analogues in 79 patients with colorectal cancer, pancreatic carcinoma, gastric cancer, carcinoid tumor, or insulinoma.. Visualization of gastrointestinal tumors and metastases was obtained with radiolabeled VIP. Binding of the labeled peptide by primary tumors and metastases was visible shortly after the injection and was still demonstrable at 24 hours. In patients with colorectal adenocarcinomas, primary or recurrent tumors were visualized in 10 of 10, liver metastases in 15 of 18, lung metastases in 2 of 3, and lymph-node metastases in 4 of 4. Primary pancreatic adenocarcinomas were visualized by imaging in 10 of 12 patients, and liver metastases were seen in 7 of 7. Primary or recurrent gastric adenocarcinomas were visualized in 5 of 5 patients, and liver metastases were seen in 2 of 2 patients. VIP scans were positive in 9 of 10 patients with carcinoid tumors and in 4 of 4 patients with insulinomas. Some tumors with positive VIP scans were also visualized with somatostatin analogues (4 of 17 colorectal adenocarcinomas, 8 of 9 carcinoids, and 2 of 2 insulinomas). In vitro binding studies confirmed the presence of VIP receptors on gastrointestinal tumors.. Scanning with radiolabeled VIP can visualize intestinal tumors and metastases that express receptors for VIP.

Topics: Adenocarcinoma; Carcinoid Tumor; Colorectal Neoplasms; Female; Gastrointestinal Neoplasms; Humans; Insulinoma; Iodine Radioisotopes; Male; Octreotide; Pancreatic Neoplasms; Radionuclide Imaging; Receptors, Somatostatin; Receptors, Vasoactive Intestinal Peptide; Stomach Neoplasms; Vasoactive Intestinal Peptide

Physiological roles of enterohormones such as secretion, absorption and digestion were supported by clinical data. Overexpression of cholecystokinin (CCK), neurotensin (NT) and vasoactive intestinal peptide (VIP) receptors occur in gastrointestinal (GI) malignancies. The aim of the paper was to compare plasma levels of CCK, peptide YY (PYY), VIP and NT in patients with gastrointestinal malignancies and healthy controls. The study included 80 patients (37 men and 43 women) with GI malignancies (20 with gastric and 60 with colorectal cancers). Median age of the patients was 62.9 years (range: 40-85 years). Control group was comprised of 30 healthy persons with median age 59.8 years (range: 40-82 years). Fasting plasma concentrations of CKK, PYY, NT, and VIP were determined at rest, using ELISA kits for automated systems. Comparative analysis of enterohormone levels in patients with various types of gastrointestinal malignancies demonstrated presence of some cancer-specific alterations. Patients with gastric cancers presented with lower plasma concentrations of CCK than healthy controls and individuals from colorectal cancers (p = 0.02). The highest plasma concentrations of neurotensin was found in colorectal cancer patients in comparison to gastric (p = 0.02). The plasma levels of VIP observed in gastric cancer group were lower than in colorectal cancer patients (p = 0.01). Patients with GI malignancies may present with tumor-specific alterations in plasma enterohormone levels.

Topics: Adult; Aged; Aged, 80 and over; Cholecystokinin; Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Neurotensin; Peptide YY; Stomach; Stomach Neoplasms; Vasoactive Intestinal Peptide

The VPAC1 receptor, a member of the vasoactive intestinal peptide receptors (VIPRs), is overexpressed in the most frequently occurring malignant tumors and plays a major role in the progression and angiogenesis of a number of malignancies. Recently, phage display has become widely used for many applications, including ligand generation for targeted imaging, drug delivery and therapy. In this work, we developed a panning procedure using a phage display peptide library to select a peptide that specifically binds to the VPAC1 receptor to develop a novel targeted probe for molecular imaging and therapy.. CHO-K1 cells stably expressing VPAC1 receptors (CHO-K1/VPAC1 cells) were used to select a VPAC1-binding peptide from a 12-mer phage peptide library. DNA sequencing and homologous analysis of the randomly selected phage clones were performed. A cellular ELISA was used to determine the most selectively binding peptide for further investigation. Binding specificity to the VPAC1 receptor was analyzed by competitive inhibition ELISA and flow cytometry. The binding ability of the selected peptide to CHO-K1/VPAC1 cells and colorectal cancer (CRC) cell lines was confirmed using fluorescence microscopy and flow cytometry.. A significant enrichment of phages that specifically bound to CHO-K1/VPAC1 cells was obtained after four rounds of panning. Of the selected phage clones, 16 out of 60 shared the same peptide sequence, GFRFGALHEYNS, which we termed the VP2 peptide. VP2 and vasoactive intestinal peptide (VIP) competitively bound to the VPAC1 receptor. More importantly, we confirmed that VP2 specifically bound to CHO-K1/VPAC1 cells and several CRC cell lines.. Our results demonstrate that the VP2 peptide could specifically bind to VPAC1 receptor and several CRC cell lines. And VP2 peptide may be a potential candidate to be developed as a useful diagnostic molecular imaging probe for early detection of CRC.

Topics: Amino Acid Sequence; Animals; Binding, Competitive; Cell Line, Tumor; CHO Cells; Colorectal Neoplasms; Cricetinae; Flow Cytometry; Gene Expression; Humans; Ligands; Microscopy, Fluorescence; Molecular Imaging; Molecular Sequence Data; Peptide Library; Peptides; Protein Binding; Receptors, Vasoactive Intestinal Polypeptide, Type I; Sequence Analysis, DNA; Transfection; Vasoactive Intestinal Peptide

A primary mucinous colorectal adenocarcinoma tissue with signet-ring cells, as revealed after histological evaluation, was examined ultrastructurally. The authors also analyzed the immunohistochemical data of the tissue for serotonin, vasoactive intestinal polypeptide (VIP), bombesin, somatostatin, and glucagon, using the peroxidase anti-peroxidase (PAP) method and the immunogold labeling method for light and electron microscope, respectively. Electron microscopically mucinous adenocarcinoma was characterized by the formation of small lumen. Adenocarcinoma cells were full of mucous granules of varying electron density, providing a good environment for the tumor cells to grow. They also exhibited a significant loss of microvilli and intracytoplasmic junctions, which could allow the cells to disseminate. Signet-ring cells were located in the basal site of the ducts or in the lamina propria and appeared neoplastic, with mucin accumulation intracellularly and an eccentric crescent-shaped nucleus. The cytoplasmic organelles were decreased and at the periphery of the cell. The PAP method demonstrated that these cells were strongly positive for bombesin and also positive for vasointestinal polypeptide (VIP). The immunogold method detected bombesin immunoreactivity in the vacuoles as well as in other cytoplasmic membranes, whereas VIP was localized mainly in the plasma membrane. The location of signet-ring cells combined with the immunoreactivity for bombesin and VIP indicated that signet-ring cells were of neuroendocrine origin and probably dedifferentiated enterochromaffin-like endocrine cells. These findings have implications for understanding the biological behavior of these composite malignant tumors and could help in the knowledge of the origin of signet-ring cells.

Topics: Adult; Biomarkers, Tumor; Bombesin; Carcinoma, Signet Ring Cell; Colorectal Neoplasms; Cystadenocarcinoma, Mucinous; Cytoplasmic Granules; Female; Glucagon; Humans; Immunoenzyme Techniques; Microscopy, Electron, Transmission; Microvilli; Mucins; Serotonin; Somatostatin; Vasoactive Intestinal Peptide

In an effort to develop a peptide-based radiopharmaceutical for the detection of tumors overexpressed vasoactive intestinal peptide receptors with positron emission tomography, we have prepared a novel [R(8,15,21), L17]-VIP peptide for 18F-labeling. This peptide inhibited 125I-VIP binding to rats lung membranes with high affinity [half-maximal inhibitory concentrations (IC50) of 0.12 nm]. Additionally, [R(8,15,21), L17]-VIP showed higher stability than native vasoactive intestinal peptide in vivo of mice. With N-succinimidyl 4-[18F] fluorobenzoate as labeling prosthetic group, [18F]FB-[R(8,15,21), L17]-VIP was obtained in >99% radiochemical purity within 100 min in decay-for-corrected radiochemical yield of 33.6 +/- 3% (n = 5) and a specific radioactivity 255 GBq/micromol at the end of synthesis. Stability of [18F]FB-[R(8,15,21), L17]-VIP in vitro and in vivo were investigated. Biodistribution of this trace was carried out in mice with induced C26 colorectal tumor. Fast clearance of [18F]FB-[R(8,15,21), L17]-VIP from non-target tissues and specific uptakes by tumors realized higher tumor-to-muscle ratio (3.55) and tumor-to-blood ratio (2.37) 60 min postinjection. Clear difference was observed between the blocking and unblocking experiments in biodistribution and whole body radioautography. [18F]FB-[R(8,15,21), L17]-VIP has demonstrated its potential for diagnosing tumors overexpressed vasoactive intestinal peptide receptors both in vitro and in vivo.

Topics: Amino Acid Sequence; Animals; Cell Membrane; Colorectal Neoplasms; Iodine Radioisotopes; Lung; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Neoplasms; Peptides; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Rats, Inbred Strains; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide

The aim of this study was to investigate the ultrastructural appearance of mirror biopsies from primary colorectal adenocarcinomas combined with serotonin, vasoactive intestinal polypeptide, bombesin, somatostatin and glucagon expression in order to clarify the histology and immunology of these tissues compared with colorectal adenocarcinomas. The investigation was carried out in 90 cases of mirror biopsies by electron microscope immunocytochemistry. The ultrastructural study revealed that some cases (30%) of mirror biopsies were characterized by the presence of intracellular changes compared to normal tissues. The most significant of them were the presence of swollen abnormal mitochondria and the increased number of the secretory cells. The above enzymic and secretory changes were confirmed by electron immunogold results. Bombesin and VIP appeared to be located in enterochromaffin-like (ECL) endocrine cells primarily responsible for the production of serotonin. Somatostatin was located in D cells while we found numerous glucagon (EG) immunoreactive cells. In conclusion, low somatostatin expression, high glucagon and serotonin expression and the ectopic secretion of VIP and bombesin neuropeptides in mirror biopsies indicate the preneoplastic nature of these tissues and may be useful for the optimal treatment of patients with colorectal adenocarcinoma.

Topics: Adenocarcinoma; Biopsy; Bombesin; Cell Differentiation; Colorectal Neoplasms; Glucagon; Humans; Immunohistochemistry; Microscopy, Electron; Microscopy, Electron, Transmission; Neuropeptides; Serotonin; Somatostatin; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) is considered to influence cellular proliferation through its action on adenylate cyclase. This study examined VIP in the tumor-neighboring mucosa (TM) and remote normal mucosa (RM) in patients with colorectal carcinoma, and explored its relationship to tumor stage.. Immunohistochemical staining of VIP, using the avidinbiotin peroxidase complex technique, was performed on TM and RM from 55 patients, surgically resected colorectal carcinomas. The VIP immunoreactivity in the lamina propria (LP) of TM and RM was semiquantitatively graded, according to the density of VIP immunoreactive fibrous strands, and correlated with clinical characteristics, pathological findings, and tumor stage.. VIP immunoreactivity in the LP of TM and RM was found mainly as fibrous strands, some of which were nerve fibers. A few pericryptal myofibroblasts also showed VIP immunoreactivity. The VIP immunoreactivity in the LP was significantly greater in TM than in RM. The VIP immunoreactivity in the LP of TM was marginally greater in lesions with distant metastasis. The VIP immunoreactivity in the LP of RM was significantly greater in lesions with deeper wall penetration, in those with lymph node metastasis, and in those at more advanced stages.. These results suggest a possible trophic role of VIP in the progression of colorectal carcinoma, or enhanced VIP secretion secondary to or in parallel with the progression of carcinoma.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Colorectal Neoplasms; Disease Progression; Female; Humans; Immunohistochemistry; Intestinal Mucosa; Male; Middle Aged; Neoplasm Staging; Observer Variation; Vasoactive Intestinal Peptide

Early and reliable diagnosis of colorectal cancer continues to be demanding and challenging. Colorectal cancer cells express Vasoactive Intestinal Peptide (VIP) receptors in high density. We have prepared a VIP analog (TP3654), labeled it with (99m)Tc, and evaluated it in experimental animals as an agent for imaging colorectal cancer. The tissue distribution of (99m)Tc-TP3654 has been compared with that of (111)In-DTPA-Octreotide and (99m)Tc-anti-CEA scan in nude mice bearing human colorectal cancer LS174T. Finally, pharmacokinetic and tissue distribution studies of (99m)Tc-TP3654 have been performed in four normal human volunteers. Data suggest that (99m)Tc-TP3654 can be prepared efficiently without loss of its receptor specificity and biological activity. Although the 24 hr tumor uptake of (99m)Tc-TP3654 in the animal model used was modest (0.21 +/- 0.07% I.D./g), the tissue distribution profile was more favorable than that of (111)In-DTPA-Octreotide or (99m)Tc-anti-CEA scan. Human studies indicated that (99m)Tc-TP3654 had no adverse effect in any subject. Within 24 hours, approximately 70% of the injected dose cleared through the kidneys, and approximately 20% through the hepatobiliary system. In these non-fasting volunteers hepatobiliary clearance was slow and in cancer patients tumor uptake was rapid. Data suggest that (99m)Tc-TP3654 is a promising agent for imaging colorectal cancer.

Topics: Colorectal Neoplasms; Humans; Indium Radioisotopes; Kidney; Octreotide; Oligopeptides; Quality Control; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Vasoactive Intestinal Peptide; Technetium; Tissue Distribution; Vasoactive Intestinal Peptide

The perivascular innervation of arterioles in colorectal cancer and adjacent submucosa was investigated.. Neurotransmitter markers, neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH), were studied and immunoreactivity was compared with that of control normal tissue.. There was absence of perivascular nerves within tumours and loss of perivascular innervation in the submucosa adjacent to the tumour. The pattern of loss varied for different transmitters. The loss was progressively greater with advancing tumour stage for NPY (controls 95%, Dukes' A 68%, Dukes>> B 13%, Dukes' C 6%) and VIP (50%, 23%, 20%, 17%). For TH there was extensive loss of innervation around tumours of all stages (69%, 5%, 7%, 0%). SP immunoreactive peri-arteriolar nerves were similar in control tissue (39%) and tissue adjacent to Dukes' A tumours (40%) but diminished to 19% and 0% in tissue adjacent to Dukes' B and C tumours, respectively. In none of the tissues was CGRP immunoreactivity above 4%. The mean distance over which there was reduced NPY immunoreactivity from the tumour edge was 2.43 mm for Dukes' A/B tumours compared with 7.20 mm for Dukes' C tumours; for VIP immunoreactivity this distance was 5.22 mm for Dukes' A/B tumours and 5.52 mm for Dukes' C tumours.. The progressive loss, both in terms of vascular nerve immunoreactivity and distance from the tumour edge with tumour grade, suggests that the tumour itself may influence neural integrity in perivascular plexuses, perhaps via the secretion of an inhibitory factor.

Topics: Aged; Aged, 80 and over; Arterioles; Biomarkers, Tumor; Calcitonin Gene-Related Peptide; Colon; Colorectal Neoplasms; Female; Humans; Male; Neoplasm Staging; Neuropeptide Y; Rectum; Substance P; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

Human adenocarcinomas of the gastroenteropancreatic system overexpress vasoactive intestinal peptide (VIP) receptors and therefore represent logical diagnostic targets for receptor scintigraphy. Using iodine-123 labelled VIP, the newly employed diagnostic procedure termed VIP receptor scintigraphy (VIP-RS) appears to detect tumour tissue, especially pancreatic metastatic tumours, in almost all cases. So far, however, only a single centre has demonstrated convincing positive results. The aim of this study was to compare the sensitivity and specificity of VIP-RS with those of computer tomography (CT) and transabdominal ultrasound in patients with extensive pancreatic metastatic adenocarcinomas and neuroendocrine tumours. VIP was radiolabelled with carrier-free 123I using the chloramine T-method and preparative high-performance liquid chromatography for purification. Patients with metastatic pancreatic (n=12) and colorectal (n=3) carcinomas (adenocarcinoma: n=13, neuroendocrine tumour: n=2) were studied by VIP-RS, CT, ultrasound and, in one case, also by radioligand receptor autoradiography. Carrier-free radioiodinated VIP of maximum specific radioactivity maintained a high biological activity as determined by cAMP formation in receptor-expressing tumour cell lines. Intravenous injection of 123I-VIP did not cause any side-effects. Biodistribution, determined over 24 h, was high in the lungs and low in abdominal organs. Although all patients had extensive metastatic disease as evidenced by CT and ultrasound, VIP-RS was unable to detect either primaries or metastases in these patients. Only in two patients could a significant uptake of radiolabel be detected in organs directly infiltrated by the primary. To exclude false-negative findings, tumour tissue in one patient with a large primary, undetectable by VIP-RS, was analysed by radioligand receptor autoradiography and shown to be receptor positive. Moreover, in vitro receptor determinations showed that pancreatic carcinomas usually have fewer VIP receptors than the normal tissues to which they metastasize, like the liver. It is concluded that VIP can be radioactively labelled with maximum specific radioactivity while maintaining biological activity. Intravenous administration leads to a biodistribution almost identical to that reported previously. However, in contrast to these reports, very low sensitivity and specificity were observed for the detection of pancreatic cancers. In retrospect, these findings are

Topics: Adenocarcinoma; Adult; Aged; Colorectal Neoplasms; Female; Humans; Iodine Radioisotopes; Liver; Male; Middle Aged; Neuroendocrine Tumors; Pancreatic Neoplasms; Radionuclide Imaging; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) is a naturally occurring 28-amino acid peptide with a wide range of biological activities. Recent reports suggest that VIP receptors are expressed on a variety of malignant tumor cells and that the receptor density is higher than for somatostatin. Our aims were to label VIP with 99mTc--a generator-produced, inexpensive radionuclide that possesses ideal characteristics for scintigraphic imaging--and to evaluate 99mTc-VIP for bioactivity and its ability to detect experimental tumors.. VIP28 was modified at the carboxy terminus by the addition of four amino acids that provided an N4 configuration for a strong chelation of 99mTc. To eliminate steric hindrance, 4-aminobutyric acid (Aba) was used as a spacer. VIP28 was labeled with 1251, which served as a control. Biological activity of the modified VIP28 agonist (TP3654) was examined in vitro using a cell-binding assay and an opossum internal anal sphincter (IAS) smooth muscle relaxivity assay. Tissue distribution studies were performed at 4 and 24 h after injection, and receptor-blocking assays were also performed in nude mice bearing human colorectal cancer LS174T. Blood clearance was examined in normal Sprague-Dawley rats.. The yield of 99mTc-TP3654 was quantitative, and the yields of 125I-VIP and 1251-TP3654 were >90%. All in vitro data strongly suggested that the biological activity of 99mTc-TP3654 agonist was equivalent to that of VIP28. As the time after injection increased, radioactivity in all tissues decreased, except in the receptor-enriched tumor (P = 0.84) and in the lungs (P = 0.78). The tumor uptake (0.23 percentage injected dose per gram of tissue [%ID/g]) was several-fold higher than 125I-VIP (0.06 %ID/g) at 24 h after injection in the similar system. In mice treated with unlabeled VIP or TP3654, the uptake of 99mTc-TP3654 decreased in all VIP receptor-rich tissues except the kidneys. The blood clearance was biphasic; the alpha half-time was 5 min and the beta half-time was approximately 120 min.. VIP28 was modified and successfully labeled with 99mTc. The results of all in vitro examinations indicated that the biological activity of TP3654 was equivalent to that of native VIP28 and tumor binding was receptor specific.

Topics: Animals; Binding, Competitive; Colorectal Neoplasms; Humans; In Vitro Techniques; Iodine Radioisotopes; Mice; Mice, Nude; Muscle Contraction; Muscle, Smooth; Neoplasm Transplantation; Oligopeptides; Opossums; Radionuclide Imaging; Rats; Rats, Sprague-Dawley; Receptors, Vasoactive Intestinal Peptide; Technetium; Transplantation, Heterologous; Tumor Cells, Cultured; Vasoactive Intestinal Peptide

To clarify whether advanced colorectal carcinomas possess an amphocrine nature and produce both pancreatic and gut neurohormonal polypeptide and epithelial mucin in comparison with surrounding colorectal mucosa.. Retrospective analysis of paraffin-embedded specimens from 100 cases of colorectal carcinoma (39 colonic and 61 rectal) and surrounding mucosa, with histochemical and immunohistochemical studies.. The immunoreactivity of the carcinomas and surrounding mucosa by the labeled streptavidin-biotin complex method for polyclonal rabbit antibody against human vasoactive intestinal polypeptide, pancreatic polypeptide, and somatostatin was 61%, 59%, and 82% respectively; that of mucosa neighboring immunoreactive tumors was 87%, 85%, and 90%; and that of mucosa neighboring nonimmunoreactive tumors was 67%, 63% and 61%. Double staining for different types of neurohormonal polypeptide revealed that most carcinoma cells had a multiendocrine nature, and a number of neurohormonal polypeptide--positive and epithelial mucin-positive carcinoma cells (amphocrine cells) were found in almost every histological type of carcinoma by double staining for immunoreactivity and periodic acid-Schiff reaction or mucicarmin.. Colorectal carcinomas exhibit not only multiendocrine characteristics, producing various types of neurohormonal polypeptide, but also amphocrine characteristics of different grades, and most tumor-neighboring crypt cells possess those characteristics, too. We concluded that these characteristics of colorectal carcinomas may be related to their origin as multipotential endodermal stem cells.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Intestinal Mucosa; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Retrospective Studies; Somatostatin; Vasoactive Intestinal Peptide

Specimens of the sigmoid colon were obtained from male and female patients (n = 11) with carcinoma of the colon or rectum and studied immunohistochemically for vasoactive intestinal polypeptide-, somatostatin-, substance P-, neuropeptide Y-, calcitonin gene-related peptide-, met- and leu-enkephalin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-containing nerves. In the subdivisions of the submucous plexus (namely, Schabadasch's, Meissner's, and the intermediate plexuses), substance P- and vasoactive intestinal polypeptide-immunoreactive nerve fibers were the most numerous, and equal densities of these nerves were found in all three layers. In contrast, few neuropeptide Y-, met-enkephalin-, leu-enkephalin-, calcitonin gene-related peptide-, somatostatin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-immunoreactive nerves were found in these regions. The nerve cell bodies of the submucous plexus contained vasoactive intestinal polypeptide, substance P, leu-enkephalin, somatostatin, and 5-hydroxytryptamine but not neuropeptide Y, met-enkephalin, calcitonin gene-related peptide, and dopamine beta-hydroxylase. Vasoactive intestinal polypeptide-containing nerve cell bodies were found in all three subdivisions. Substance P-, leu-enkephalin-, and somatostatin-immunoreactive nerve cell bodies were found in Schabadasch's plexus and the intermediate region of the submucous plexus, but they were absent from Meissner's plexus; 5-hydroxytryptamine-containing nerve cell bodies were only observed in Schabadasch's plexus. The possible function of the neuropeptide-, dopamine beta-hydroxylase-, and 5-hydroxytryptamine-containing neurons in the different layers of the submucous plexus is discussed.

Topics: Adult; Aged; Calcitonin Gene-Related Peptide; Colon, Sigmoid; Colorectal Neoplasms; Dopamine beta-Hydroxylase; Enkephalins; Female; Fluorescent Antibody Technique; Humans; Male; Middle Aged; Neurons; Neuropeptide Y; Neuropeptides; Serotonin; Somatostatin; Submucous Plexus; Substance P; Vasoactive Intestinal Peptide

Topics: Colorectal Neoplasms; Humans; Immunotherapy; Intestinal Mucosa; Neuropeptides; Somatostatin; T-Lymphocytes; Vasoactive Intestinal Peptide