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At least 217 records · Page 12Linked to original sources
PubMed2001

Importance of early screening and prophylactic thyroidectomy in asymptomatic nonindex RET germline carriers.

Genetic testing for RET germline mutations affords rapid identification of germline carriers, offering the prospect of cure before C-cell hyperplasia (CCH) has progressed to medullary thyroid carcinoma (MTC). Although nonindex RET mutation carriers have a better prognosis than do the index patients, it remains to be ascertained whether age represents a risk factor for MTC when screening patients. The current institutional study (October 1994 through June 1999) was set up to compare asymptomatic nonindex patients who were grouped by age: < 20 years and > or = 20 years. Inclusion criteria were confirmed RET mutations in the germline, with no MTC being more advanced than pT1pN1M0. Adult patients (> or = 20 years) had MTC significantly more often (84% vs. 43%), significantly larger tumors (5 mm vs. 3 mm), and significantly higher basal calcitonin levels preoperatively (78.0 vs. 9.7 pg/ml) than their pediatric/adolescent counterparts (< 20 years). There was a close correlation between pT1 MTC and an elevated basal serum calcitonin level (r = 0.67; Spearman's rho). All three patients with lymph node metastases from MTC had elevated basal calcitonin levels. The two groups did not differ in terms of multifocality of MTC (pT1b), lymph node involvement (pN1) or bilateral lymph node metastasis (pN1b), or preoperative stimulated and postoperative basal and stimulated serum calcitonin. Prophylactic thyroidectomy should not be postponed beyond the age of 20, and it should be performed before basal serum calcitonin has turned positive. Pathologic conversion of stimulated serum calcitonin obviously marks the time in carriers of RET germline mutations when surgery should be scheduled at the latest to be prophylactic.

Adolescent↗
PubMed2003

Concurrent lymph node metastases of medullary and papillary thyroid carcinoma in a case with RET oncogene germline mutation.

We report the case of a 72 yr-old woman who underwent total thyroidectomy and resection of neck lymph nodes because of a firm nodule in the right lobe, which was consistent with medullary thyroid carcinoma (MTC) on cytological examination. Histology showed multifocal bilateral MTC; a 2 mm papillary thyroid carcinoma (PTC) was also detected in the right lobe, next to a focus of MTC; five cervical lymph nodes contained MTC. In one right perithyroidal lymph node, concurrent metastases of MTC and PTC were demonstrated. DNA analysis showed a point mutation in exon 14 at codon 804 of the RET proto-oncogene locus, as frequently found in cases of familial MTC (FMTC). To our knowledge, this case represents the first documented case of concurrent lymph node metastases of MTC and PTC in a patient with RET proto-oncogene germline mutation. We report this unique case, discuss related thyroid malignancies, and suggest possible underlying pathogenetic mechanisms.

Aged↗
PubMed2006

Medullary thyroid carcinoma: multivariate analysis of prognostic factors influencing survival.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare development of thyroid cancer with a no negligible mortality rate. Our aim was to determine factors that predict outcome in patients with MTC. METHODS: We reviewed the records of all patients with MTC (n=56) who underwent treatment at our institution between January 1990 and December 2000. Univariate and multivariate analysis of clinicopathologic predictors of MTC outcome were performed to identify subsets of patients with different probabilities in terms of overall survival, local recurrence, and distant metastases. RESULTS: Multivariate analysis demonstrated that a statistically significant decrease in overall survival is associated with T4b tumours (p=0.06), the presence of distant metastases at the time of presentation (p=0.033), lymphatic invasion (p=0.099), and postoperative treatment (p=0.045). CONCLUSIONS: The analysis of survival curves of patients with MTC shows that the occurrence of locoregional and distant metastases occurs preferentially within the first 5 years, which identifies this as a crucial period for follow-up. In this series of patients with MTC, the tumours classified as T4b, metastases at presentation, the presence of lymphovascular invasion, and postoperative treatment were the most important prognostic features. At present, there is no available beneficial adjuvant therapy. However, as the development of molecular therapy progresses, it should be tested in clinical trials with the purpose of achievement of novel targeted therapies for selected MTC patients with risk factors.

Adult↗
PubMedDate not supplied

Clinical manifestations of familial medullary thyroid carcinoma.

We conducted a large-scale nation-wide questionnaire survey to ascertain the status of familial medullary thyroid carcinoma (MTC) in Japan in 2002. Out of a total of 271 MTC cases (male to female ratio 1:1.4), multiple endocrine neoplasia (MEN) 2A accounted for 83 cases (30.6%), familial MTC (FMTC) for 14 cases (5.1%), MEN for 11 cases (4.1%), and sporadic MTC for 163 cases (60.1%). Mean age at the time of diagnosis was 35.6 in MEN2A, 34.6 in FMTC, 30.5 in MEN2B, and 47.6 in sporadic MTC. Forty-five percent of MEN2A patients had pheochromocytoma and 11% of MEN2A patients had parathyroid disorders when MTC was diagnosed. Finally, the RET oncogene test yielded the largest number of initial findings that led to diagnosis of familial MTC.

Adrenal Gland Neoplasms↗
PubMed2004

Results of surgical treatment of sporadic medullary thyroid carcinoma following routine measurement of serum calcitonin.

AIM: The aim of this study was to evaluate the results of the surgical management of medullary thyroid carcinoma (MTC), following the introduction of systematic calcitonin measurement in patients referred for thyroid diseases. METHOD: We included all the patients with elevated calcitonin and MTC from January 1993 to March 2001. RESULTS: Among 8497 patients, MTC was diagnosed in 52 with a mean age of 56.1 years. Thirty-two fine needle biopsies led to diagnose MTC in 19 cases. The median basal pre-operative calcitonin level was 245 pg/ml. Elevated calcitonin serum was the only indicator of MTC in 31 patients. Fifty-one patients underwent total thyroidectomies, with lymphadenectomy in 45. Thirteen patients had lymph node involvement. Post-operatively, 40 (77%) had normal basal and pentagastrin (Pg) stimulated calcitonin serum levels, and remained normal at a mean follow-up of 5.16 years (1.8-8). CONCLUSION: Routine pre-operative measurement of calcitonin should be performed because it is often the only indicator of MTC at an early stage. This could lead to an improved MTC cure rate.

Adolescent↗
PubMed2006

Natural history, diagnosis, treatment and outcome of medullary thyroid cancer: 37 years experience on 157 patients.

AIM: The analysis of a 37-year retrospective study on diagnosis, prognostic variables, treatment and outcome of a large group of medullary thyroid cancer (MTC) patients was conducted, in order to plan a possible evidence-based management process. METHODS: Between Jan 1967 to Dec 2004, 157 consecutive MTC patients underwent surgery in our centre: 60 males and 97 females, mean age 47.3 years (range 6-79). Total thyroidectomy was performed in 143 patients (91.1%); central compartment (CC) node dissection (level VI) in 41 patients; central plus lateral compartment (LC) node dissection (levels II, III, and IV) in 82 patients. Subtotal thyroidectomy was initially performed in 14 cases: 10 of them were re-operated because of persistence of elevated serum calcitonin levels. RESULTS: After a median post-surgical follow-up of 68 months (range 2-440 months), 42.9% of patients were living disease-free, 39.8% were living with disease, 3.1% were deceased due to causes different from MTC, and 3.2% were deceased due to MTC. The overall 10-year survival rate was 72%. At uni-variate statistical analysis (a) patient's age at initial treatment (>45 years; >/=45 years), (b) sporadic vs. hereditary MTC, (c) disease stage, and (d) the extent of surgical approach resulted as significant variables. Instead, at multivariate statistical analysis, only (a) patient's age at initial diagnosis, (b) disease stage, and (c) the extent of surgery resulted as significant and independent prognostic variables influencing survival. CONCLUSION: The presence of lymph node and distant metastases at first diagnosis significantly worsened prognosis and survival rate in our series. Early diagnosis of MTC is very important, allowing complete surgical cure in Stages I and II patients. Due to the relatively bad prognosis of MTC, especially for disease Stages III and IV, it appears reasonable to recommend radical surgery including total thyroidectomy plus CC lymphoadenectomy as the treatment of choice, plus LC lymphoadenectomy in patients with palpable and/or ultrasound enlarged neck lymph nodes.

Adolescent↗
PubMed2005

Increased incidence of medullary thyroid carcinoma in patients treated for Hirschsprung's disease.

BACKGROUND/PURPOSE: Mutations of the RET proto-oncogene are responsible for the development of inherited multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma (MTC). RET mutations are encountered in patients with Hirschsprung's disease (HD). We hypothesized that the incidence of MTC is increased in patients with HD. METHODS: Patients treated for HD at the Children's Hospital, University of Helsinki, during 1939 and 1986 were surveyed for cancer using the population-based countrywide Finnish Cancer Registry from 1967 to 2000. The number of observed cancer cases and that of person-years at risk were counted. The expected number of cancer cases was extrapolated from national cancer incidence rates. To calculate the standardized incidence ratios (SIRs), the observed number of cancer cases was divided by the expected number of cancer cases. RESULTS: One hundred fifty-six patients (132 males) with HD were identified. The mean length of patient follow-up was 30.9 years. Seven cases of cancer were observed (SIR, 3.5; 95% CI, 1.4-7.3). Two patients developed MTC (SIR, 550; 95% CI, 67-2000). The cases of MTC occurred in male patients at the ages of 34 and 37 years. No patient developed pheochromocytoma. CONCLUSIONS: In this study, we report for the first time an increased risk of MTC occurring in patients treated for HD. The increased risk may be attributed to mutations of the RET proto-oncogene shared by MTC and HD. These findings warrant further studies concerning screening for MTC-type RET mutations in patients with HD.

Adolescent↗
PubMed2001

Use of a habit reversal treatment for temporomandibular pain in a minimal therapist contact format.

Previous research has suggested that a habit reversal treatment might be used effectively in a home-based minimal therapist contact (MTC) protocol to facilitate flexibility and increase treatment completion rates. Recent reviews of MTC interventions have found it to be generally efficacious, cost-effective, and generalizable. While MTC has been used for certain health-related disorders (e.g., headache), almost no research has evaluated the effectiveness of a MTC protocol with a population suffering from temporomandibular disorder (TMD). The current study utilized an oral habit reversal treatment in a MTC format in an attempt to reduce attrition and increase treatment flexibility. Twenty females suffering from TMD were randomly assigned to either a treatment (n = 10) or a wait-list control (n = 10) condition. Six individuals in each group used telephone contact while 4 used e-mail for weekly communication with the therapist. Results demonstrated that a habit reversal treatment in a MTC format led to statistically and clinically significant improvements in mean weekly pain ratings, number of pain-free days per week, and highest weekly pain ratings. Also, a significant reduction in maladaptive oral habits occurred from pre- to post-treatment and significant reductions in life stress and pain interference were observed. Results were maintained at follow-up. The implications for the use of MTC for treatment of facial pain are discussed, as are the implications of these findings for the role of oral habits in the etiology of TMD.

Adaptation, Psychological↗
PubMed2003

Focal adhesions and associated proteins in medullary thyroid carcinoma cells.

BACKGROUND: In medullary thyroid carcinoma (MTC), mutations in the RET protooncogene lead to oncogenic transformation. RET activation in other cell types has been shown to cause phosphorylation of the focal adhesion-associated proteins focal adhesion kinase (FAK), paxillin, and p130(CAS). We hypothesized that adhesion-dependent signaling might be deranged in MTC cells. METHODS: Indirect immunofluorescence was used to label beta(1) integrin, FAK, paxillin, and p130CAS. Rhodamine-labeled phalloidin was used to visualize actin microfilaments. Phosphorylated protein was detected by immunoprecipitation followed by Western blotting for phosphotyrosine. MTC cell invasiveness was quantified using a modified Boyden chamber assay. RESULTS: Clustering of beta(1) integrin, FAK, paxillin, and p130(CAS) into focal adhesions were not detected in MTC cells under any conditions, although clustering was seen as expected in control HeLa cells. Despite this failure, FAK, paxillin and p130(CAS) were all found to be phosphorylated. Actin microfilaments were generally not seen although in a few cells, small, poorly formed microfilaments could be detected. MTC cells invaded poorly as compared with highly invasive cell lines. However a clear difference was noted between invasiveness on growth factor depleted Matrigel and regular Matrigel. CONCLUSIONS: In MTC cells, focal adhesions are not seen in response to interaction with extracellular matrix. Consistent with this failure, actin microfilaments are absent or poorly formed and invasion is weak. Despite the absence of focal adhesions, focal adhesion proteins remain phosphorylated, even though in normal cells their signaling activity is dependent on focal adhesion formation. Deranged adhesion-dependent signaling may contribute to MTC pathogenesis.

Actin Cytoskeleton↗
PubMed1995

Multiple endocrine neoplasia type 2B: more than an endocrine disorder.

BACKGROUND: Multiple endocrine neoplasia type 2B (MEN 2B) is a rare disorder differentiated from MEN 2A primarily by its extraendocrine features. This report describes the clinical spectrum and outcome of MEN 2B. METHODS: Twenty-one patients underwent operation for manifestations of MEN 2B between 1970 and 1993. Median follow-up was 16.9 years. Diagnosis was made through family screening in nine, the development of medullary thyroid carcinoma (MTC) in seven, phenotypic features in four, and constipation in one. Median age at presentation of colonic dysfunction, MTC, and pheochromocytoma was 0.1, 16, and 28 years, respectively. RESULTS: Every patient had MTC. Fifteen (94%) of 16 patients undergoing primary thyroidectomies had multicentric disease, and seven (44%) had nodal metastases. Seven patients (33%) had pheochromocytoma, six bilateral and one malignant. Adrenalectomy was curative in every patient. Nineteen patients (90%) had colonic disturbances, typically chronic constipation from birth. Megacolon developed in 14 patients, and eight required colonic surgery. Every patient had the characteristic phenotype. Dominant features included neuromas of the tongue, buccal mucosa, lips, conjunctivae, and eyelids and a marfanoid habitus. Other features included high arched palate, corneal nerve thickening, and dental and skeletal abnormalities. Four patients died, two of metastatic MTC, one after operation for metastatic MTC, and one as a consequence of colonic perforation. Of 17 survivors, three have hepatic metastases from MTC, eight have nodal metastases, and six are well with normal or mildly elevated calcitonin levels. CONCLUSIONS: MEN 2B is characterized by a relatively aggressive form of MTC, bilateral pheochromocytoma, severe colonic dysfunction, and a multitude of other extraendocrine abnormalities. Early recognition of MEN 2B and early prophylactic thyroidectomy are essential. Colonic dysfunction has previously received little attention, and further investigation of the pathogenesis and treatment of this disorder is warranted.

Adolescent↗
PubMed1996

Progression of postoperative residual medullary thyroid carcinoma as monitored by plasma calcitonin levels.

BACKGROUND: Patients operated on for medullary thyroid carcinoma (MTC) frequently have persistent elevated plasma calcitonin concentrations after operation, indicating remaining tumor. The plasma calcitonin concentration in a patient with MTC roughly reflects the endogenous tumor burden. The only effective treatment for MTC is surgical. The decision about whether a patient with persistent MTC should have a repeat operation would be influenced by knowledge of the natural course of the disease. METHODS: Forty patients with persistently elevated peak plasma calcitonin concentrations after thyroidectomy for MTC were monitored for a mean of 6 years. Serial determinations of plasma calcitonin levels were obtained before and after intravenous injection of calcium and pentagastrin. RESULTS: At the first postoperative test 63% of the patients had undetectable basal calcitonin values, although their stimulated plasma calcitonin concentrations were elevated. The mean annual increase in stimulated plasma calcitonin concentrations was 117%, but plasma calcitonin concentrations were stable in three patients and decreased in one patient. Five patients are known to have experienced distant metastases. CONCLUSIONS: MTC is a progressive disease in most patients with persistent hypercalcitoninemia after thyroidectomy. Stimulated peak plasma calcitonin levels are more meaningful than basal levels in the serial postoperative evaluation of patients with persistent hypercalcitoninemia after thyroidectomy for MTC.

Adolescent↗
PubMed1998

Monitoring of C-reactive protein after allogeneic bone marrow transplantation identifies patients at risk of severe transplant-related complications and mortality.

Patterns of C-reactive protein (CRP) release were derived from frequent CRP measurements in a cohort of 66 consecutive patients receiving allogeneic bone marrow transplants (BMT) in our unit. Based on a retrospective study of clinical events occurring within the first 40 days after BMT, patients with major transplant-related complications (MTC+ group, n = 22) could be separated from those with fever or mild complications only (MTC- group, n = 44). Treatment-related mortality in the MTC+ group was significantly higher: 32 vs 0% (P < 0.001). Major complications included veno-occlusive liver disease (VOD), severe endothelial leakage syndrome (ELS), pneumonitis and acute GVHD >II. The severity of complications was reflected by the patterns of CRP release with continuously high levels preceding the maximal signs and symptoms of MTC. Univariate analysis showed that, among other variables (sex, age, disease status at transplant, +/- TBI in the conditioning regimen, +/- use of myeloid growth factors after BMT, time to reach PN >200/mm3), three factors were significantly associated with MTC: maximal levels of CRP during the post-transplant episode (CRPmax) (296.6 +/- 91.8 vs 88.9 +/- 55.8 mg/100 ml, P < 0.001), the use of unmanipulated graft (no T depletion) (46.9 vs 12.5%, P < 0.009) and the CRP level on the day of BMT (CRPo) (42.7 +/- 55.4 vs 18.2 +/- 19.5, P = 0.045). In multivariate analysis, using a stepwise logistic regression model including the same variables, CRPmax appeared to be the strongest independent variable (P < 0.001) and a reliable (94% accuracy) parameter to assess the risk of MTC. Based on this model, CRP levels of 200 and 300 mg/100 ml are associated with a risk of 48 and 94% of developing MTC, respectively. We conclude that CRP monitoring after BMT identifies patients at risk of severe transplant-related complications and mortality.

Acute Disease↗
PubMed1998

RET cooperates with RB/p53 inactivation in a somatic multi-step model for murine thyroid cancer.

Mice bred to carry germline Rb and p53 null alleles are associated with a tumor spectrum that overlaps with the inherited multiple endocrine neoplasia-1 (MEN1) and MEN2 syndromes in humans, including medullary thyroid cancer (MTC). To study the genetic basis for these tumors, we microdissected MTC specimens or obtained fresh MTC tissue from nine independent Rb(+/-) p53(+/-) mice, amplified the region of the Ret gene known to be mutated in human MTC, and detected acquired missense Ret mutations in four different mice. These mutations were localized to a group of tandem cysteines which are analogous to activating germline mutations observed in human MEN2A and familial MTC (FMTC). To determine whether the remaining wild type Rb allele was inactivated in these murine MTC samples, we subjected tumor tissue to immunohistochemical staining with an Rb antibody, and demonstrated the absence of RB staining in murine MTC, while normal tissue retained RB nuclear staining. These findings demonstrate the ability of the gene knockout model to recapitulate somatic multi-step tumorigenesis and suggest that the development of a murine neuroendocrine tumor requires mutational dysregulation within both receptor tyrosine kinase and nuclear tumor suppressor gene pathways.

Animals↗
PubMed2001

Over-representation of a germline variant in the gene encoding RET co-receptor GFRalpha-1 but not GFRalpha-2 or GFRalpha-3 in cases with sporadic medullary thyroid carcinoma.

In contrast to the hereditary form of medullary thyroid carcinoma (MTC), little is known about the etiology of sporadic MTC. Somatic gain-of-function mutations in the RET proto-oncogene, encoding a receptor tyrosine kinase, are found in an average of 40% of sporadic MTC. We analysed 31 sporadic MTC for somatic and germline variants in GFRA1, GFRA2 and GFRA3 which encode the co-receptors of RET. Although there were no somatic mutations in any of the three genes, a sequence variant (-193C>G) in the 5'-UTR of GFRA1 was found in 15% of cases. Three patients were heterozygous (het); another three patients homozygous (hom) for the G variant. The G allele was not observed in 31 race-matched normal controls. Hence, the relative frequency of this variant in sporadic MTC cases and controls differed significantly (P<0.05). Since this variant lies in the 5' UTR, likely at the transcriptional start site, we analysed for differential expression of GFRalpha-1 at the transcript and protein levels. At the mRNA level, GFRA1 was over-expressed in tumors harboring the rare variant (P=0.06). The presence of the G polymorphic allele seemed to be associated with increased expression by immunostaining for GFRalpha-1. Interestingly, cytoplasmic staining was stronger in intensity for het patients and nuclear staining predominant in hom cases. In conclusion, mutation analysis of GFRA1, GFRA2 and GFRA3 revealed over-representation of a rare variant in GFRA1 (-193C>G) in the germline of sporadic MTC cases. Our data suggest that the mechanism is related to over-expression of GFRalpha-1 and differential subcellular compartmentalization but the precise mechanism as to how it acts as a low penetrance susceptibility allele for the development of sporadic MTC remains to be elucidated.

Carcinoma, Medullary↗
PubMed2002

Cholecystokinin-B/Gastrin receptor-targeting peptides for staging and therapy of medullary thyroid cancer and other cholecystokinin-B receptor-expressing malignancies.

The high sensitivity of the pentagastrin stimulation test in detecting primary or metastatic medullary thyroid cancer (MTC) suggests a widespread expression of the corresponding receptor type on human MTC. Indeed, autoradiographic studies demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in more than 90% of MTCs, but also in a high percentage of small-cell lung cancers, stromal ovarian tumors, and potentially a variety of other tumors, including gastrointestinal adenocarcinomas, neuroendocrine tumors, and malignant glioma. The aim of our work was to develop and systematically optimize suitable radioligands for targeting CCK-B receptors in vivo and to investigate their role in the staging and therapy of MTC and other CCK-B receptor expressing malignancies. For this purpose, a variety of CCK/gastrin-related peptides, all having in common the C-terminal CCK-receptor binding tetrapeptide sequence-Trp-Met-Asp-PheNH(2) or derivatives thereof, were investigated. They were members of the gastrin or cholecystokinin families or possessed characteristics of both, which differ by the intramolecular position of a tyrosyl moiety. Their stability and affinity were studied and optimized in vitro and in vivo; their biodistribution and therapeutic efficacy were tested in preclinical models. Best tumor uptake and tumor to nontumor ratios were obtained with members of the gastrin family, because of their superior selectivity and affinity for the CCK-B receptor subtype. Radiometal-labeled derivates of minigastrin showed excellent targeting of CCK-B receptor expressing tissues in animals and healthy human volunteers. Preclinical therapy experiments in MTC-bearing animals showed significant antitumor efficacy. In a subsequent clinical study, 45 MTC patients with metastatic MTC were investigated; 23 had known and 22 had occult disease. CCK-B receptor scintigraphy was performed with (111)In-diethylenetriamine pentaacetic acid-d-Glu(1)-minigastrin. The normal organ uptake was essentially confined to the stomach (and, to a lesser extent, to the gallbladder and, in premenopausal women, to normal breast tissue) as a result of CCK-B receptor specific binding and to the kidneys, as excretory organs. All tumor manifestations known from conventional imaging were visualized as early as 1 hour postinjection, with increasing tumor to background ratios over time; at least 1 lesion was detected in 20 of 22 patients with occult disease (patient-based sensitivity, 91%). Among them were local recurrences and lymph node, pulmonary, hepatic, splenic, and bone (marrow) metastases. Eight patients with advanced metastatic disease were injected in a dose-escalation study with potentially therapeutic activities of a (90)Y-labeled minigastrin derivative at 4 to 6-week intervals (30-50 mCi/m(2) per injection for a maximum of 4 injections). Hematologic and renal toxicities were identified as the dose-limiting toxicities at the 40 and 50 mCi/m(2) levels. Two patients experienced partial remissions, and 4 experienced stabilization of their previously rapidly progressing disease. These data suggest that CCK-B receptor ligands may be a useful new class of receptor-binding peptides for diagnosis and therapy of a variety of (CCK-B receptor expressing) tumor types. They allow for sensitive and reliable staging of patients with metastatic MTC. Initial therapeutic results are promising, but nephrotoxicity is a major concern to be solved.

Animals↗
PubMed2001

Circulating calcitonin and carcinoembryonic antigen m-RNA detected by RT-PCR as tumour markers in medullary thyroid carcinoma.

Detection of local relapse or metastasis in medullary thyroid carcinoma (MTC) continue to pose a major diagnostic challenge. Besides established diagnostic studies such as serum calcitonin (CT) and carcinoembryonic antigen (CEA), molecular detection of circulating tumour cells may be an additional diagnostic tool for the early detection of disease recurrence. We performed reverse transcription-polymerase chain reaction (RT-PCR) on blood samples from patients diagnosed with MTC disease using primers specific for CT and CEA, respectively. CT mRNA was not detectable in peripheral blood of all patients with MTC (n = 11) and all controls (n = 32). CEA mRNA was significantly more often detected patients with MTC (72.7%) than in controls (34.4%; p = 0.038; Fisher exact test). With an example of a patient with MTC and massive tumour mass in the neck we demonstrate the failure of detection of CT mRNA over a period of 6 months, whereas CEA mRNA could be detected in peripheral blood of this patient. As a consequence, CT mRNA detected by RT-PCR in the peripheral blood can not be recommended as a tumour marker in MTC. However, the use of carcinoembryonic mRNA may provide a significant improvement in diagnosis of recurrent disease in MTC.

Biomarkers, Tumor↗
PubMed2006

Amplification of molecular traffic control in catalytic grains with novel channel topology design.

We investigate the conditions for reactivity enhancement of catalytic processes in porous solids by the use of molecular traffic control (MTC). With dynamic Monte-Carlo simulations and continuous-time master equation theory applied to the high concentration regime, we obtain a quantitative description of the MTC effect for a network of intersecting single-file channels in a wide range of grain parameters and for optimal external operating conditions. Implementing the concept of MTC in models with specially designed alternating bimodal channels, we find the efficiency ratio (compared with a topologically and structurally similar reference system without MTC) to be enhanced with increasing grain diameter, a property verified for the first time for a MTC system. Even for short intersection channels, MTC leads to a reactivity enhancement of up to approximately 65%. This suggests that MTC may significantly enhance the efficiency of a catalytic process for small as well as large porous particles with a suitably chosen binary channel topology.

Journal Article↗
PubMed1998

Calcitonin receptor mRNA is expressed in human medullary thyroid carcinoma.

We recently reported the presence of a truncated form (h-CTR2) of the human calcitonin receptor (CTR) in TT cells, a cell line derived from medullary thyroid carcinoma (MTC). This form (h-CTR2), characterized by the absence of 16 amino acids in the first intracellular domain, was also detected in two cases of MTC. In the present study we determined the expression of CTR mRNA in a larger sample, representative of the different clinical forms of MTC, and in normal thyroid. h-CTR2 was expressed in all MTC specimens (both sporadic and familial) and in the normal thyroid samples. The expression of the receptor mRNA was higher in MTC compared with normal thyroid. Moreover, CT and CTR mRNA levels were modified significantly during proliferation. This result suggests that CT may be involved in proliferation of MTC via autocrine/paracrine regulation. Calcitonin secretion by MTC may play a role in the development and spread of these tumors.

Carcinoma, Medullary↗