Evaluation of the Specificity of the Leukocyte Migration Inhibition Test against Histologically Homologous and Heterologous Neoplastic Antigens in Cancer Patients

1981 ◽  
Vol 67 (3) ◽  
pp. 169-175 ◽  
Author(s):  
Giovanni Mantovani ◽  
Maria A. Manca ◽  
Francesco Cossu ◽  
Ernesto Proto ◽  
Guglielmo Taglieri ◽  
...  

The aim of the present study was to verify whether the CMI response of the host's lymphocytes is directed towards tumor-associated antigens (TAA) specific for each histological type of tumor. The leucocyte migration inhibition (LMI) test was selected for this purpose, utilizing the cancer patients' leucocytes and, as neoplastic antigens, formalin-fixed cells of surgically removed cancer tissue. Two hundred and eighteen patients were studied, 110 of whom were affected by breast cancer, 48 by digestive tract and 60 by laryngeal cancer. The total amount of tests performed was 278. The leucocytes of 93 normal subjects were tested against the different tissues' cancer antigens, as were the leucocytes of 41 patients with cancer of different organs tested against the corresponding normal tissues' antigens. The breast cancer patients (122 tests performed) showed 82.35 % positive tests against homologous antigen, 72.72 % and 95.24 % against heterologous (digestive tract and laryngeal cancer, respectively) antigens. The digestive tract cancer patients (69 tests performed) showed 70.27 % positive tests against homologous, 66.66 % and 43.48 % against heterologous antigens (breast and laryngeal cancer, respectively). The laryngeal cancer patients (87 tests performed) showed 74.29 % positive tests against homologous, 38.10 % and 80.65 % against heterologous antigens (breast and digestive tract, respectively). The results led to the conclusion that the LMI test response of cancer patients was not « tissue specific »: the test did not discriminate between the homologous and the heterologous cancer antigens, and it seems that the response was not directed towards specific TAA but only towards wide-range or « group » TAA, shared by several types of tumors.

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Toru Hanamura ◽  
Koichi Ohno ◽  
Shinya Hokibara ◽  
Hideki Murasawa ◽  
Toshitsugu Nakamura ◽  
...  

Abstract Background Recent preclinical data suggest that androgen receptor (AR) signaling plays a significant role in subsets of breast cancer. Clinical trials testing AR-targeting therapies in breast cancer have been conducted. Assessment of AR-signal in breast cancer tissue maybe useful for treatment selections. Prostate specific antigen (PSA) is the product of an androgen-responsive gene. Serum PSA (sPSA) can be detected in women by a highly sensitive assay although the concentration is much lower than that observed in males. We investigated if sPSA reflects tumor biology, including AR signaling in breast cancer patients. Methods In this study, 132 healthy controls and 144 breast cancer patients were enrolled. sPSA was evaluated by the chemiluminescent enzyme immunoassay (CLEIA) method. Correlations between sPSA and the various clinicopathological factors were analyzed. Results In post-menopausal state, sPSA detection rate was significantly higher in breast cancer patients compared with controls (27.4% vs 11.3%: p = 0.0090), but not in the whole cohort (29.2% vs 25.8%: p = 0.5265) or pre-menopausal subgroup (37.0% vs 42.6%: p = 0.6231). In post-menopausal breast cancer cases, higher sPSA value was associated with clinic-pathological factors including the expression of AR protein in primary legion. In a correlation analysis of quantitative data limited to post-menopausal metastatic breast cancer (MBC), sPSA was positively, albeit weakly correlated with clinic-pathological features including serum testosterone levels and AR positivity. Conclusions Our data suggest that sPSA may reflect tumor biological properties including AR activity in post-menopausal breast cancer.


2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 94-94
Author(s):  
Raquel E. Reinbolt ◽  
Xueliang Jeff Pan ◽  
Kaitlin K. Wandell ◽  
Robert Pilarski ◽  
Rachel M. Layman ◽  
...  

94 Background: Weight gain concerns breast cancer patients, can impact quality of life, may lead to therapy non-adherence, and is associated with increased recurrence risk and mortality. Early placebo-controlled trials did not identify a clear correlation between Tamoxifen (TAM) and weight gain; gain due to aromatase inhibitors (AIs) is not well characterized. We hypothesized that weight gain occurs more frequently than previously reported in breast cancer patients receiving endocrine therapy. Methods: This is a retrospective chart review investigating body mass index (BMI) change in women after breast cancer therapy. Patients with early stage breast cancer and whom had BMI and treatment data (at least 90 days) from 2003-2012 were identified in The Columbus Breast Cancer Tissue Bank. Patients were separated by treatment received: chemotherapy with and without endocrine therapy vs. endocrine therapy alone (including both TAM and AIs) vs. no other treatment. Results: A total of 970 subjects were included in the analysis. At diagnosis and/or treatment initiation, patients’ mean BMI was 29.2 ± 7.0 kg/m2; mean age 53.7± 11.6 years; and average length of therapy/follow up per patient, 1833 days (range 90-3,990). Patients who received an AI alone had significantly decreased BMIs during therapy (-0.65± 0.29 kg/m2, p = 0.025), whereas patients receiving chemotherapy alone, chemotherapy with TAM, or TAM followed by AI therapy, had significantly increased BMIs (0.51 ± 0.25, 0.73 ± 0.26, 1.01 ± 0.51 kg/m2; p = 0.039, 0.005, 0.045, respectively). Both older age and a higher BMI at diagnosis were associated with a significantly greater decline in BMI over treatment time (p < 0.001 and p < 0.001, respectively). In a multivariate regression model, after adjusting for age and initial BMI effect, the BMI change noted among different treatment groups was no longer significantly different (p = 0.43). BMI change was not statistically associated with treatment length (p = 0.26). Conclusions: Our review of a large, early stage breast cancer patient cohort showed no association between weight gain and endocrine therapy after adjusting for the effect of initial BMI and age at diagnosis. Additional study is needed to identify other factors impacting weight in this population.


2005 ◽  
Vol 20 (2) ◽  
pp. 103-111 ◽  
Author(s):  
J. Rodríguez ◽  
J. Vízquez ◽  
M.D. Corte ◽  
M. Lamelas ◽  
M. Bongera ◽  
...  

Background Cathepsin D is the proteolytic enzyme most frequently implicated as a prognostic factor in primary breast cancer. In the present study we evaluated by means of an immunoradiometric assay the tumor content of this protease in primary breast cancer, its relationship with tumor-related clinical and pathological parameters, and its prognostic significance in a large series of breast cancer patients. Method The study comprised 1033 women with histologically established invasive breast cancer. Cathepsin D was measured in cytosol samples by means of an immunoradiometric assay to determine the total amount of cathepsin D (52 kDa, 48 kDa and 34 kDa). Evaluation of relapse-free survival and cause-specific survival was performed in the group of 1003 patients without evidence of metastasis at the time of initial diagnosis. The median follow-up of the patients who were free of recurrence was 54 months. Results Cathepsin D levels showed a wide range among the studied tumors (n=1033; median (range) 41 (0.9–2504) pmol/mg protein). Statistical analysis showed that the median cathepsin D levels were considerably higher in large tumors (T2–4) than in smaller ones (T1) (p=0.017), as well as in node-positive than in node-negative tumors (p=0.004). Cathepsin D levels were also higher in ductal tumors than in the other histological types (p=0.001), as well as in moderately or poorly differentiated tumors (p<0.001). Likewise, the median value of the protease was significantly higher in ER or PgR-positive tumors than in hormone receptor-negative ones (p=0.011 and p=0.004, respectively), as well as in aneuploid tumors than in diploid tumors (p=0.029). Multivariate analysis demonstrated that elevated cathepsin D levels (>59 pmol/mg protein) were notably associated with a shorter cause-specific survival in the whole group of patients with breast cancer, as well as in the subgroup of node-positive patients (p<0.05). Conclusions This study suggests that elevated intratumoral cathepsin D levels may identify a subset of node-positive breast cancer patients showing a high probability of earlier death.


2015 ◽  
Vol 1 (1) ◽  
pp. 23-30
Author(s):  
Sri Indah Aruminingsih ◽  
Lina Choridah ◽  
Yana Supriatna

Background: Tamoxifen is a Selective Estrogen Reseptor Modulators, serves as an anti-estrogen to block the e?ects of estrogen on breast cancer tissue. Tamoxifen interferes with fat metabolism which lead to fatty liver. Ultrasonography is main modality to detect the presence of fatty liver, which is divided into degrees of 0, 1, 2 and 3. Fat infltration into liver blood vessels causes a decrease in intrahepatic vascular compliance which can be examined using Doppler hepatic vein spectral ultrasound, into a triphasic, biphasic or monophasic waveform.Objectives: To compare the degree of fatty liver and hepatic vein spectral waveform and its correlation in ultrasonography of breast cancer patients with and without tamoxifen therapy.Materials and Methods: Observational cross-sectional study with non-random consecutive sampling. This study used questionnaires and grey-scale ultrasound examination of the liver and right hepatic vein spectral Doppler ultrasound. Statistical analysis used was K-S test.Results: Mode of breast cancer diagnosed age range was 50-60 y.o. and the youngest was 28 y.o. None of the subjects was obese. The mean use of tamoxifen was 19+5,87 months. There is an increase in the incidency of degree 1 and 3 fatty liver in breast cancer patients with tamoxifen therapy, but this was not statistically signifcant. Hepatic vein spectral abnormalities with monophasic waveforms also increased in tamoxifen therapy compared without tamoxifen therapy, but this was not statistically signifcant.Conclusions: Increased incidency of degree 1 and 3 fatty liver and abnormal spectral monophasic waveform in breast cancer patients with tamoxifen were not statistically signifcant. There was no signifcant correlation between the incidency of degree of fatty liver and hepatic vein spectral waveform.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shreeya Kotecha ◽  
Marie N. Lebot ◽  
Bhudsaban Sukkarn ◽  
Graham Ball ◽  
Paul M. Moseley ◽  
...  

AbstractDopamine and cAMP regulated phosphoprotein 32 kDa (DARPP-32) also known as phosphoprotein phosphatase-1 regulatory subunit 1B and encoded by the PPP1R1B gene is an inhibitor of protein phosphatase-1 and protein kinase A. DARPP-32 is expressed in a wide range of epithelial cells and some solid tumours; however, its role in breast cancer is only partially defined. DARPP-32 expression was determined using immunohistochemistry in two independent cohorts of early stage invasive breast cancer patients (discovery n = 1352; validation n = 1655), and 112 HER2 positive breast cancer patients treated with trastuzumab and adjuvant chemotherapy. PPP1R1B mRNA expression was assessed in the METABRIC cohort (n = 1980), using artificial neural network analysis to identify associated genes. In the discovery cohort, low nuclear expression of DARPP-32 was significantly associated with shorter survival (P = 0.041), which was independent of other prognostic variables (P = 0.019). In the validation cohort, low cytoplasmic and nuclear expression was significantly associated with shorter survival (both P = 0.002), with cytoplasmic expression independent of other prognostic variables (P = 0.023). Stronger associations with survival in oestrogen receptor (ER) positive disease were observed. In patients treated with trastuzumab, low nuclear expression was significantly associated with adverse progression-free survival (P = 0.031). In the METABRIC cohort, low PPP1R1B expression was associated with shortened survival of ER positive patients. Expression of CDC42 and GRB7, amongst others, were associated with PPP1R1B expression. This data suggests a role for DARPP-32 as a prognostic marker with clinical utility in breast cancer.


1977 ◽  
Vol 63 (1) ◽  
pp. 97-107 ◽  
Author(s):  
José Garcia Puche ◽  
Silvana Canevari ◽  
Giuseppe Fossati ◽  
Giuseppe Della Porta ◽  
Paolo Vezzoni

The conditions for a 51Cr release assay on cell lines derived from human solid tumors were determined by using a rabbit antihuman antiserum with human AB serum as source of complement. By this assay 38 sera collected before and after surgery from 19 breast cancer patients and 28 sera from 12 melanoma patients and 16 healthy donors were tested on 3 lines derived from breast cancer tissue and 1 line derived from normal breast tissue. Ten of the breast cancer patients had lymph node metastases and 9 did not. Positive reactions were obtained from 4 breast cancer patients, all with lymph node metastases, and from 1 healthy donor. In a second experiment, 58 coded sera belonging to 4 different groups of cancer and non-cancer individuals were assayed on a colonic cancer line (HT-29), and 33 and 20 of them were also tested on a melanoma line (MeWo) and on a breast cancer line (MaCa 13), respectively. Positive responses were few, and were more frequently observed among transfused than non-transfused patients.


2006 ◽  
Vol 103 (2) ◽  
pp. 185-195 ◽  
Author(s):  
Mogens Groenvold ◽  
Peter M. Fayers ◽  
Morten Aagard Petersen ◽  
Mirjam A. G. Sprangers ◽  
Neil K. Aaronson ◽  
...  

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