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PubMed2003

The usefulness of CEA and/or CA19-9 in monitoring for recurrence in gastric cancer patients: a prospective clinical study.

BACKGROUND: Many studies on postoperative carcinoembryonic antigen (CEA) and/or carbohydrate antigen (CA)19-9 monitoring after operation for gastric cancer have been reported, but most have been retrospective. METHODS: A nationwide observational study was implemented in 135 leading institutions in Japan to evaluate the significance of CEA and/or CA19-9 in postoperative monitoring for recurrence in patients with advanced gastric cancer. Three hundred and twenty-one patients examined in this analysis underwent radical gastrectomy at one of Japan's leading institutions between November 1993 and March 1996 and had been followed up for at least 5 years. Serum levels of CEA and CA19-9 were examined preoperatively and every 3 months postoperatively, with diagnostic imagings, such as chest X-ray, computed tomography (CT), and ultrasonography also being performed every 3 months. RESULTS: Recurrence was observed in 120 patients (peritoneum, 48; liver 16; lymph node, 16; multiple sites, 25; and others, 12). Sensitivities of CEA and either CEA or CA19-9, or both, for recurrence were 65.8% and 85.0%, respectively, both of which values were significantly higher than the preoperative positivities (28.3% and 45.0%, respectively). In most patients with high preoperative levels CEA and/or CA19-9, these tumor markers increased again at recurrence. Recurrent diseases were detected between 5 months after detection by diagnostic imagings and 12 months before detection by diagnostic imagings (mean of 3.1 +/- 3.6 months before detection by diagnostic imagings) and between 10 months after detection by diagnostic imagings and 13 months before detection by diagnostic imagings (mean of 2.2 +/- 3.9 months before detection by diagnostic imagings) by CEA and CA19-9 monitorings, respectively. CONCLUSION: These results suggest that CEA and/or CA19-9 monitoring after operation was useful to predict the recurrence of gastric cancer, especially in almost all the patients with high preoperative levels of these markers.

Adenocarcinoma↗
PubMed2004

Correlation between serum HER-2 oncoprotein and patients with breast cancer.

OBJECTIVE: To detect serum HER-2 oncoprotein levels in patients with operable and metastatic breast cancers, and to study the correlations between serum HER-2 level and lymph node status as well as other clinical parameters. METHODS: A total of 120 women were studied consisting of 10 healthy volunteers, 31 benign breast disease, 53 operable breast cancer, and 26 metastatic breast cancer patients. The levels of serum HER-2 were measured using an enzyme-liked immunosorbent assay (ELISA). RESULTS: The mean serum HER-2 levels were 9.6 +/- 1.5 ng/mL in healthy volunteers, 11.9 +/- 1.6 ng/mL in benign breast disease, 13.2 +/- 4.2 ng/mL in operable breast cancer, and 30.5 +/- 30.8 ng/mL in metastatic breast cancer patients. The former is much lower than the latter three (P = 0.02, 0.001, 0.03, respectively). If using 15 ng/mL as a normal baseline, elevated serum HER-2 levels were observed in none of the healthy volunteers as well as patients with benign disease, but in 18.9% (10/53) operable breast cancer patients and 61.5% (16/26) metastatic patients. In patients with operable breast cancer, there was a positive correlation between serum concentrations of HER-2 and the size of primary tumor (P < 0.05), whereas there was no correlation between serum concentration and axillary lymph node or estrogen receptor status. In patients with metastatic disease, there was no correlation with site of metastases (P > 0.05). CONCLUSION: Serum HER-2 level was strongly correlated with tumor loads and clinical stages, thus acting as a promising predictor of cancer recurrence in breast cancer patients.

Biomarkers, Tumor↗
PubMed1999

Signals involved in the early TH1/TH2 polarization of an immune response depending on the type of antigen.

BACKGROUND: The early production of distinct cytokines by epidermal cells (ECs) in response to antigen exposure may govern the development of TH1 -like immune responses, such as contact sensitivity, or TH2 -like immune responses, such as IgE-dependent allergies of the immediate type, depending on the type of antigen. OBJECTIVE: The aim of this study was to compare the signals induced by protein allergens with those induced by haptens in ECs and subsequently in local draining lymph node cells (LNCs) or splenocytes. METHODS: BALB/c mice were primed in vivo with the protein allergens ovalbumin or birch pollen or the haptens 2, 4-dinitrofluorobenzene or trinitrochlorbenzene, respectively, and cytokine and immunoglobulin secretions of responding splenocytes were measured by ELISA after in vitro coculture with ECs. Induction of cytokine mRNA expression in ECs and LNCs was analyzed by reverse transcriptase-PCR. RESULTS: In the presence of protein allergens, ECs enhance the induction of a TH2 immune response (IL-4 and IgE production of splenocytes), whereas a TH1 immune response (IFN-gamma and IgG2a production) was only induced in the context of haptens. Heat inactivation of ovalbumin did not diminish the development of a TH2 immune response. One direct effect of antigen on ECs was the earlier expression of IL-10 mRNA after stimulation with protein allergens (30 minutes) than with haptens (2 hours) in vitro. By using an in vivo approach, sensitization of the skin with trinitrochlorbenzene, but not with ovalbumin, resulted in an early induction of IL-1beta, IL-12p40, and IFN-gamma mRNA in LNCs, whereas IL-18 was induced by both. CONCLUSION: These data indicate that the type of antigen strongly influences the type of immune response by eliciting distinct signals already in the epithelium.

Allergens↗
PubMed2006

Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients.

PURPOSE: To evaluate the predictive and prognostic value of peripheral blood cytokeratin-19 (CK-19) mRNA-positive cells in axillary lymph node-negative breast cancer patients. PATIENTS AND METHODS: Peripheral blood was obtained from 167 node-negative breast cancer patients before the initiation of any systemic adjuvant therapy, and was analyzed for the presence of CK-19 mRNA-positive cells using a real time polymerase chain reaction assay. The association with known prognostic factors and the effect of CK-19 mRNA-positive cells on patients' prognosis was investigated. RESULTS: CK-19 mRNA-positive cells were detected in the blood of 36 (21.6%) of the 167 patients. There was no correlation between the detection of CK-19 mRNA-positive cells in the peripheral blood and the various known pathologic and clinical prognostic factors; only overexpression of HER2 receptor (score 2+/3+) on the primary tumor was associated with a higher incidence of CK-19 mRNA-positive cell detection (P = .033). Multivariate analysis revealed that detection of peripheral blood CK-19 mRNA-positive cells was associated with early clinical relapse (P < .00001) and disease-related death (P = .008). CONCLUSION: Detection of peripheral-blood CK-19 mRNA-positive cells is an independent predictive and prognostic factor for reduced disease-free interval and overall survival, respectively, in node-negative breast cancer patients.

Adult↗
PubMed1989

Enhanced anti-tumor effects of recombinant human tumor necrosis factor plus VP-16 on metastatic renal cell carcinoma in a xenograft model.

A nude mouse renal subcapsular and subcutaneous implantation xenograft model utilizing the SN12C human renal carcinoma cell line was investigated. In the absence of treatment, renal subcapsular implantation of SN12C resulted in metastatic spread (lung, liver and lymph nodes) and death of all animals. Radical nephrectomy of the tumor-bearing kidney after various periods of tumor implantation demonstrated that surgery alone after 18 days of tumor growth resulted in no statistically significant increase in survival with 100% of the nephrectomized animals succumbing to local recurrence and distant metastases. Recombinant human tumor necrosis factor (rTNF) and VP16 (etoposide), both well known cytotoxic and cytostatic anticancer agents, were tested singly and in combination against this metastatic model of human renal adenocarcinoma. Single agent rTNF or VP16 therapy after radical nephrectomy demonstrated only minimal efficacy with no significant decrease in local recurrence and distant metastases as compared to nephrectomy only control animals. In contrast, the combination of rTNF plus VP16 when given after nephrectomy resulted in a significant decrease in local recurrence and no gross evidence of metastasis in any animal. Subcutaneously growing SN12C tumor nodules were also treated with the same rTNF, VP16 and combination regimens. Regression in tumor size was noted only in the combination treatment group. rTNF or VP16, as single agents, demonstrated only slight growth inhibition that was not statistically significant. These results suggest that by combining TNF plus VP16, a synergistic enhancement of antineoplastic activity against local as well as metastatic human renal cell carcinoma can be produced.

Animals↗
PubMed1989

[The immunohistochemical growth fraction (Ki-67) of breast cancers: relations to tumor spread, tumor morphology and receptor testing].

245 breast cancer tissues were analysed immunohistochemically, using monoclonal antibody Ki-67, which spezifically reacts with a nuclear antigen of proliferating cells and represents the so-called growth fraction. According to the number of positive cells, three Ki-score categories (I-III) were established. The results were compared with prognostic variables (Histological grading, DNA-cytophotometry), staging parameters, immunocytochemical (ER-ICA, mPRI), and biochemical (DCC) hormone receptor assay. We found a good correlation between Ki-67 and grading (Bloom and Richardson): G 1-tumors had small growth fractions, in contrast to G-III carcinoma, which showed a high percentage of Ki-Score III. Receptor negative cases had a large growth fraction and receptorpositive ones showed an uniform distribution. The comparison between Ki-67 and tumor spread or DNA-Cytophotometry showed no correlation. The majority of 31 recurrent tumors not only had a large number of positive cells, but also a definite dependence was found between Ki-Score and length of the disease-free period. Ki-67 seems to be an important immunohistochemical marker of breast cancer, which contributes to the individual assessment of the disease and can possibly give predictions on tumor development and response to radiation and systemic therapy.

Adult↗
PubMed2006

UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 6 (ppGalNAc-T6) mRNA as a potential new marker for detection of bone marrow-disseminated breast cancer cells.

The evaluation of disseminated epithelial tumor cells in patients with early stages of breast cancer has generated considerable interest because of its potential association with poor clinical outcome. Considering that O-glycosylation pathways are frequently altered in breast cancer, we performed this work to evaluate the potential usefulness of UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) (a family of glycosyltransferases which catalyze the first key step of mucin-type O-glycosylation) to detect disseminated cells in bone marrow samples from patients with operable breast cancer. Using RT-PCR assays, we studied the gene expression of 9 enzymes (ppGalNAc-T1-T9). Among the ppGalNAc-Ts expressed by breast tumors (-T1, -T2, -T3, -T6 and -T7), the best specificity (negative results on all PBMN cell samples from healthy donors) was shown for ppGalNAc-T6. Thus, we selected this enzyme as a target gene for further evaluation. ppGalNAc-T6 mRNA was found in 22/25 (88%) breast cancer samples, in all 3 human breast cancer cell lines evaluated (MCF-7, ZR75-1 and T47D), in 1/30 (3%) PBMN cells and 0/19 bone marrow samples obtained from patients without cancer. Using this method, 22/61 (36%) patients with breast cancer, who underwent curative surgery, showed positive ppGalNAc-T6 mRNA in bone marrow aspirates obtained prior to surgery, including 11/34 patients with stage-I or -II, without histopathological lymph node involvement. In a preliminary follow-up evaluation, 19/61 patients experienced recurrence of the disease. ppGalNAc-T6 was positive in 11/19 (57.9%) of these patients. Interestingly, in the group of patients without lymph node involvement, disease recurrence was observed in 54.5% of patients who showed ppGalNAc-T6 mRNA-positive bone marrow aspirates and only in 4.3% of patients when ppGalNAc-T6 was negative (p = 0.014). These results indicate that ppGalNAc-T6 mRNA could be a specific marker applicable to the molecular diagnosis of breast cancer cells dissemination.

Biomarkers, Tumor↗
PubMedDate not supplied

Expression of survivin and matrix metalloproteinases in adenocarcinoma and squamous cell carcinoma of the uterine cervix.

Cervical cancer can be classified into two histological types: squamous cell carcinoma (SCA) and adenocarcinoma (ACA). Reportedly ACA has poorer prognoses, metastasizes more easily to lymph nodes, and is more resistant to radiotherapy than SCA. To clarify the cause of characteristic differences between these histological types, we examined the expressions of apoptosis inhibiting and tumor-invasion related factors in both histological types. We reviewed the 34 cases of cervical cancer (17 ACA, 17 SCA) that had surgery as their initial treatment at Osaka City University Medical School Hospital between 1996 and 2001. The differences of survivin, and matrix metalloproteinase (MMP-2, and MMP-7) expressions between both histological types were immunohistochemically assayed, and the correlation between the expression of each protein and clinicopathological characteristics was analyzed. Survivin was expressed significantly stronger in ACA cases (p=0.035). The number of patients who expressed MMP-2 and MMP-7 simultaneously was significantly higher in SCA cases (p=0.039). MMP-2 and MMP-7 had tendencies to be expressed stronger in SCA (p=0.057 and p=0.084, respectively). These results suggest that the differences of the expression of survivin (an apoptosis inhibiting factor), MMP-2, and MMP-7 (tumor-invasion related factors) between ACA and SCA were causes of the characteristic differences between the two histological types.

Adenocarcinoma↗
PubMed2005

Local cytokine responses in Dictyocaulus viviparus infection.

The high degree of immunity induced by the bovine lungworm, Dictyocaulus viviparus, makes it an ideal model in which to study nematode-induced protective immune responses. Here, cytokine responses were measured over the course of an experimental infection of D. viviparus. Local cytokine messenger RNA (mRNA) transcripts were measured in lung parenchyma, tracheal rings and draining lymph nodes using semi-quantitative reverse transcriptase-polymerase chain reaction. Responses were measured in animals necropsied at 15, 22 and 43 days post-infection (DPI). The responses elicited at these time points were compared with cytokine levels observed in uninfected animals. Interleukin (IL)-4, IL-5, IL-10, IL-12p35, IL-13 and interferon gamma (IFNgamma) mRNA levels were measured in duplicate at each site. By 42 DPI, very few parasites were recovered, either from faeces or lungs. Transcripts of all cytokines increased in the lung parenchyma, tracheal rings and caudal mesenteric lymph nodes by 15 DPI. The response was rapid and peaked during the time of larval migration through the lungs. By 42 DPI, expression levels of most cytokines were reduced to levels similar to, or below, base line values measured in uninfected animals. Highest levels of IL-10, IL-12p35, IL-13 and IFNgamma transcript were measured in the bronchial lymph nodes of uninfected animals. IgG1 levels were negatively correlated with expression levels of all cytokines. The results demonstrate that a mixed cytokine response occurs over the course of a primary infection during which the parasites were eliminated by day 43 DPI. These results agree with those obtained for other helminths in cattle and challenge the hypothesis that polarised Th2 responses are essential for protection against nematodes in this species. These observations are important in the development of recombinant vaccines, particularly when considering adjuvant choice.

Animals↗
PubMedDate not supplied

Immune responses in the lung and local lymph node of A/J mice to intranasal sensitization and challenge with adjuvant-free ovalbumin.

Pathologic features of IgE-mediated allergic airway diseases include airway infiltration of inflammatory cells (eg, lymphocytes, plasma cells, and eosinophils) and mucous cell metaplasia (MCM) in airway epithelium. CD4(+) T lymphocytes, specifically those producing a type 2 (Th2) cytokine profile, are necessary for the induction of IgE-mediated allergic airway responses. Most experimental models of IgE-mediated allergic airway disease use systemic (eg, intraperitoneal) administration of an allergen coupled with an adjuvant to sensitize animals. Cytokine changes are measured in a number of ways including in bronchoalveolar lavage fluid (BALF) or lymph node cells stimulated ex vivo. The primary objective of this study was to test the hypothesis that intranasal sensitization and challenge of mice with ovalbumin in the absence of an adjuvant will induce the pathologic features that are characteristic of IgE-mediated allergic airway disease. Another objective was to determine if intranasal delivery of this allergen will result in the induction of a profile of cytokine gene expression in the lung and tracheobronchial (TB) lymph node, that is typical of immunologic changes associated with IgE-mediated allergic airway disease. Only mice that were intranasally sensitized and challenged with ovalbumin exhibited pulmonary lesions that included marked MCM in the respiratory epithelium lining the nasal and pulmonary airways, and an associated mixed inflammatory cell influx consisting of lymphocytes, plasma cells and eosinophils. Ovalbumin-treated mice also exhibited enhanced expression of the Th2 cytokine mRNAs IL-4, IL-5, IL-10, and IL-13 in the lung and IL-4 in the TB lymph node, and concurrent increases in ovalbumin-specific IgE in the serum. The results of this study indicate that A/J mice intranasally instilled with ovalbumin without adjuvant have the hallmark histopathologic and immunologic features of IgE-mediated allergic airway disease of humans.

Adjuvants, Immunologic↗
PubMed1992

Follicular non-Hodgkin's lymphoma cell adhesion to normal germinal centers and neoplastic follicles involves very late antigen-4 and vascular cell adhesion molecule-1.

Follicular lymphomas recapitulate the architecture of germinal centers (GCs) of normal secondary lymphoid follicles. Using an in vitro binding assay, it has recently been demonstrated that the normal B lymphocytes bind to GCs. This interaction is mediated by a receptor-ligand pair consisting of the beta 1 integrin very late antigen 4 (VLA-4) on the B cell, and the vascular cell adhesion molecule-1 (VCAM-1) expressed on follicular dendritic cells (FDC). Considering the similarities between follicular lymphomas and normal GCs, the adhesive interaction of follicular non-Hodgkin's lymphoma (NHL) cells and GCs was examined. Cells isolated from 16 of 24 cases of follicular NHL bound to normal GCs. Neoplastic follicles could similarly support the binding of follicular NHL cells. This adhesion was inhibited by monoclonal antibodies (MoAbs) directed against VLA-4 and VCAM-1. This supports the hypothesis that the neoplastic follicles used the identical adhesive interactions responsible, at least in part, for the localization of normal B cells to GCs. Adhesion receptors have an important role in the regulation of normal lymphoid cell proliferation, differentiation, and localization. Therefore, an understanding of the adhesive interaction of follicular NHL cells with GCs may provide insight into the clinical and biologic behavior of these diseases.

Antibodies, Monoclonal↗
PubMed1998

Expression of platelet-derived endothelial cell growth factor in oral and oropharyngeal carcinoma.

Platelet-derived endothelial cell growth factor (PD-ECGF) was isolated as an endothelial cell mitogen from platelets. In this study, we investigated the expression of PD-ECGF and counted microvessels in 58 oral and oropharyngeal squamous cell carcinoma (SCC) specimens by an immunohistochemical technique to examine their prognostic significance and performed tumor in vitro sensitivity to 5-fluorouracil (5-FU) and cisplatin as determined by a bioluminescence assay of the ATP values of tumor cells after continuous exposure. The percentage of PD-ECGF-positive tumor cells (PD-ECGF score) was correlated with the frequency of the recurrence of disease (P=0.0043) but not with sex, tumor size, metastasis, or clinical stage. Overall survival of the high PD-ECGF expression group (>40% PD-ECGF score) was shorter than the low expression (<40%) group (P=0.0365). Vessel count was correlated with lymph node metastasis and clinical stage. The survival of patients with hypervascularity (more than the median of intratumor vessel counts, >82) was shorter than that of those with hypovascularity (vessel count <81, P=0.0446). However, there was no association between PD-ECGF expression and vessel count. Cox proportional multivariate analysis showed that PD-ECGF expression was the most significant independent prognostic indicator for overall survival. The susceptibility to 5-FU cytotoxicity in the extremely high PD-ECGF expression groups (>70% of PD-ECGF score) was significantly higher than that in the low group, whereas there was no difference in their sensitivity to cisplatin. These results showed that carcinoma cells with high PD-ECGF expression were sensitive to 5-FU in spite of poor prognosis. These data provide further information when deciding on adjuvant therapy for oral and oropharyngeal SCCs.

Analysis of Variance↗
PubMed1997

Methyl-p-hydroxyphenyllactate-esterase activity in breast cancer: a potentially new prognostic factor in short-term follow-up.

We assayed methyl-p-hydroxyphenyllactate esterase (MeHPLAase) activity in 48 cases of primary breast cancer. MeHPLAase activity did not show significant correlation with estrogen receptor and progesterone receptor levels. No significant relationship was found between enzymatic activity and tumor diameter, lymph node status, mitotic activity, degree of nuclear differentiation, and proportion of the S-phase fraction. During the follow-up period (median, 18.8 months; range, 6-69 months), recurrences were observed in 18 of 48 (37%) cases. The Weibull survival regression model using the enzymatic activity as a continuous covariate showed that levels of enzymatic activity were directly associated with the risk of recurrence (P = 0.02). Assuming the mean value of enzymatic activity as the cutoff value, we found a statistically significant relationship between high MeHPLAase activity and shorter recurrence-free survival. On multivariate analysis, MeHPLAase activity proved to be an independent factor for predicting a short period of recurrence-free survival.

Adult↗
PubMed1996

Silicon tissue assays: a comparison of nonaugmented cadaveric and augmented patient levels.

Tissue silicon assays were performed on 10 nonaugmented cadavers and 25 augmented women to confirm our previous cadaveric data and to establish silicon levels at local and distant sites in augmented women undergoing explant and further reconstruction. All assays were performed by inductively coupled plasma atomic emissions spectroscopy (ICP-AES). Cadaveric tissues were sampled from six sites: liver, spleen, breast, nipple, axilla (soft tissue and nodes), and subcutaneous tissue (abdominal). Augmented women undergoing explant surgery had a portion of their implant capsule, breast tissue, and for those undergoing autogenous reconstruction, a portion of the autogenous donor site or distant tissue sampled. Twenty-four women had silicone implants; one had saline. Results revealed baseline silicon levels in all 10 non-augmented cadavers. These results were equivalent to our previous data, confirming the validity of these baseline data. Silicon tissue levels in the 25 augmented women revealed elevated levels within the implant capsule and surrounding breast tissue. However, silicon levels obtained from distant sites in augmented women were equivalent to the baseline nonaugmented cadaveric levels. There was no correlation between intact or ruptured implants and symptoms of collagen-vascular disease. In conclusion, study validates our original data of baseline silicon levels in nonaugmented cadavers. Contrary to what some may perceive as silicone floating throughout the body, we have found elevated levels around the implant only, and levels at distant tissue sites were equivalent to the baseline cadaveric data.

Abdomen↗
PubMed2006

Technetium-99m-sestamibi subtraction scintigraphy vs. ultrasonography combined with a rapid parathyroid hormone assay in parathyroid aspirates in preoperative localization of parathyroid adenomas and in directing surgical approach.

OBJECTIVE: To determine the sensitivity and positive predictive value (PPV) of subtraction scintigraphy (SS) vs. ultrasonography (US) of the neck combined with rapid intact parathyroid hormone (iPTH) assay in US-guided fine-needle parathyroid aspirates in preoperative localization of parathyroid adenomas and in directing surgical approach. DESIGN: The results of SS for localization of parathyroid adenoma were determined in 121 patients with primary hyperparathyroidism (pHPT) and compared with findings at surgery and with the results of US alone (in patients without nodular goitre) and US in combination with the iPTH assay in US-guided fine-needle aspirates (FNAs) of suspicious parathyroid lesions (in patients with concomitant nodular goitre). PATIENTS: All 121 patients had biochemically documented pHPT; all were referred for first-time surgery. MEASUREMENTS: SS was performed with 99mTc-sestamibi and 99mTc-pertechnetate. High-resolution US of the neck was performed by a single endocrine surgeon and combined with US-guided FNAs of suspicious parathyroid lesions in all patients with nodular goitre (n = 43). RESULTS: The sensitivity and PPV of SS were significantly higher in patients without vs. with goitre (89.3% and 95.7%vs. 74.3% and 76.5%, respectively; P < 0.001). The sensitivity and PPV of US were significantly higher in patients without vs. with goitre (96% and 97.3%vs. 67.7% and 71.9%, respectively; P < 0.001). The iPTH assay of US-guided FNAs of suspicious parathyroid lesions in patients with nodular goitre significantly improved both the sensitivity and PPV of US imaging (90.7% and 100%, respectively), allowing for an accurate choice of surgical approach in 118 (97.5%) of 121 patients. SS was more accurate than US alone in detection of ectopic parathyroid adenomas. However, US alone was characterized by a higher sensitivity in detection of small parathyroid adenomas (< 500 mg) at typical sites (P < 0.01). CONCLUSIONS: Both the sensitivity and PPV of SS and US alone are comparable, with significantly less accurate results obtained in patients with goitre. In cases of equivocal results of US and/or in patients with concomitant goitre, an iPTH assay in US-guided FNAs of suspicious parathyroid lesions may be used to establish the nature of the mass, distinguish between parathyroid and nonparathyroid tissue (goitre, lymph nodes) and improve the accuracy of US parathyroid imaging, allowing for successful directing of surgical approach in a majority of patients.

Adenoma↗
PubMedDate not supplied

Studies on the minimum requirements for in vitro "cure" of tumor cells by cytotoxic T lymphocytes.

DBA/2-derived P815 tumor cells form progressively growing tumors when injected into the anterior chamber (AC) of normal BALB/c eyes. By contrast, P815 cells injected into the subconjunctival (SCon) space of BALB/c mice are promptly rejected. Despite these very different outcomes, both AC and SCon tumors elicit an equal clonal expansion of tumor-specific precursor cytotoxic T cells (pTc) within the draining cervical lymph nodes. Moreover, tumor-specific pTc migrate systemically and infiltrate both AC and SCon tumor-containing eyes. The present study explores the hypothesis that pTc generated in response to AC P815 tumors are less efficient "killers" than their SCon counterparts. To address this issue pTc were restimulated in vitro in the presence of exogenous lymphokines to initiate the terminal differentiation of pTc into fully functional cytotoxic T cells (Tc). Then an assay was developed to evaluate the capacity of AC and SCon CD8+ Tc to eliminate P815 tumor cells growing in vitro, i.e., achieve a "cure." This assay established the day tumor cells were completely eliminated (cure), as well as the rate of tumor cell removal. Using this approach it has been learned that pTc harvested from AC and SCon tumor-bearing mice have the same potential for eliminating P815 tumor cells in vitro. Moreover, the efficiency of achieving an in vitro tumor "cure" was found to be remarkably enhanced if exogenous lymphokines, as a surrogate source of T cell "help," were included in the cultures at the time effector lymphocytes were added to the proliferating tumor target cells. This latter finding emphasizes the need for sustained availability of helper factors in order to maximize the efficiency with which Tc can eliminate tumor cells. We interpret the results to mean that successful rejection of tumors in vivo is likely to turn upon (a) arrival of tumor-specific pTc at the tumor site, (b) delivery of "help" that promotes the terminal conversion of these cells into Tc, and (c) sustained presence of "help" which promotes the efficiency of immune elimination of tumor cells. Since equally large numbers of P815-specific pTc enter AC and SCon tumor sites in BALB/c mice, the failure of rejection in the former may be due to an inability of the host to provide immediate and sustained local T cell help. Implications of these studies for the development of immunotherapies for intraocular tumors are discussed.

Animals↗
PubMed1998

Prognostic significance of methyl-p-hydroxy-phenyllactate-esterase activity in laryngeal squamous cell carcinoma.

We assayed methyl-p-hydroxyphenyllactate esterase (MeHPLAase) activity in 63 cases of primary laryngeal squamous cell carcinoma. MeHPLAase activity did not show any correlation with oestrogen, progesterone and epidermal growth factor (EGF) receptor levels. No significant relationship was found between MeHPLAase activity and age, sex, tumour site, T classification, stage of disease and EGFR status, whereas a significant inverse relationship was found between enzymatic activity and neck lymph node positivity at presentation. The median value of MeHPLAase activity tended to be higher in tumours with low histopathological grade than in those with high histopathological grade. During the follow-up period (median 50 months, range 2-90 months) locoregional recurrences were observed in 31 out of 63 (49%) cases. At the end of the study, 27 out of 63 (43%) patients had died of cancer. Cox univariate analysis using MeHPLAase activity as a continuous covariate showed that the levels of enzymatic activity were inversely associated with the risk of death and relapse. Assuming the mean value of enzymatic activity as the cut-off value, we found a statistically significant relationship between high MeHPLAase activity and longer relapse-free and overall survival. MeHPLAase activity status retained its prognostic significance also in the lymph node-negative subgroup of patients. On multivariate analysis, both EGFR and MeHPLAase activity proved to be independent factors for predicting a short relapse and the overall survival.

Carboxylic Ester Hydrolases↗
PubMed2005

Quantification of melanoma micrometastases in sentinel lymph nodes using real-time RT-PCR.

Detection of micrometastases in the regional tumor-draining lymph nodes is critical for staging and prognosis in melanoma patients. We applied a quantitative multiple-marker RT-PCR assay to improve the detection of occult melanoma cells in the sentinel lymph node (SLN). From 139 patients with primary cutaneous melanoma who underwent sentinel lymphadenectomy, a total of 235 SLN were assessed for Melan-A and tyrosinase expression by real-time quantitative RT-PCR. Twenty-three patients (17%) were positive by histopathology and expressed messenger RNA of one or two markers. Of the patients with histopathologically negative SLN 39 (28%) were reclassified by positive RT-PCR. Patients were examined for tumor recurrences during a median follow-up period of 29 mo. Tumor recurrences were demonstrated in eight patients (35%) with histopathologically positive SLN, in four patients (10%) with submicroscopic tumor cells detected exclusively by real-time RT-PCR, and in none of the patients negative by both methods. The differences in recurrence rates were statistically significant (p=0.01). These data indicate that real-time quantitative RT-PCR for the detection of minimal residual melanoma in SLN improves the prediction of disease-free survival.

Antigens, Neoplasm↗