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Results for “Local Lymph Node Assay”

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PubMed2006

Elevated E2F1 inhibits transcription of the androgen receptor in metastatic hormone-resistant prostate cancer.

Activation of E2F transcription factors, through disruption of the retinoblastoma (Rb) tumor-suppressor gene, is a key event in the development of many human cancers. Previously, we showed that homozygous deletion of Rb in a prostate tissue recombination model exhibits increased E2F activity, activation of E2F-target genes, and increased susceptibility to hormonal carcinogenesis. In this study, we examined the expression of E2F1 in 667 prostate tissue cores and compared it with the expression of the androgen receptor (AR), a marker of prostate epithelial differentiation, using tissue microarray analysis. We show that E2F1 expression is low in benign and localized prostate cancer, modestly elevated in metastatic lymph nodes from hormone-naïve patients, and significantly elevated in metastatic tissues from hormone-resistant prostate cancer patients (P = 0.0006). In contrast, strong AR expression was detected in benign prostate (83%), localized prostate cancer (100%), and lymph node metastasis (80%), but decreased to 40% in metastatic hormone-resistant prostate cancer (P = 0.004). Semiquantitative reverse transcription-PCR analysis showed elevated E2F1 mRNA levels and increased levels of the E2F-target genes dihyrofolate reductase and proliferating cell nuclear antigen in metastatic hormone-independent prostate cancer cases compared with benign tissues. To identify a role of E2F1 in hormone-independent prostate cancer, we examined whether E2F1 can regulate AR expression. We show that exogenous expression of E2F1 significantly inhibited AR mRNA and AR protein levels in prostate epithelial cells. E2F1 also inhibited an AR promoter-luciferase construct that was dependent on the transactivation domain of E2F1. Furthermore, using chromatin immunoprecipitation assays, we show that E2F1 and the pocket protein family members p107 and p130 bind to the AR promoter in vivo. Taken together, these results show that elevated E2F1, through its ability to repress AR transcription, may contribute to the progression of hormone-independent prostate cancer.

Autopsy↗

PubMed1984

Restorative effects of thymosin polypeptides on purified protein derivative--dependent migration inhibition factor production by the peripheral blood lymphocytes of adult thymectomized guinea pigs.

Thymosin fraction 5 restored the capacity of peripheral blood lymphocytes (PBL) from thymectomized adult guinea pigs sensitized with purified protein derivative (PPD) to produce migration inhibition factor (MIF) as measured in an agarose droplet microassay with peritoneal exudate cells. PBL from sham-thymectomized and normal PPD-sensitized guinea pigs did not lose their capacity to make MIF in response to PPD and were unaffected by thymosin polypeptides. Splenic and lymph node lymphocytes of thymectomized guinea pigs retained their antigen responsivity , suggesting that thymectomy did not affect fully matured, localized memory cells, but caused an accumulation in the circulation of partially matured, antigen-sensitive lymphocytes that could release MIF only in the presence of thymic factors. Various thymosin polypeptides were tested in this system and only thymosin alpha 1, an acidic polypeptide of 28 amino acid residues, showed consistent activity. This polypeptide, which has a molecular weight of 3,108, did not inhibit macrophage migration by itself, but 10-1,000 ng/ml was able to completely restore the MIF-producing capability of PBL from thymectomized guinea pigs. A standardized method for pooling and cryopreserving guinea pig PBL was developed, allowing multiple assays to be performed with a single pool of cells. The specificity of this bioassay system has made it a useful tool in evaluating the thymosin alpha 1 activity present in various thymosin preparations, and in validating biological activity of thymosin alpha 1 preparations made by synthetic or recombinant DNA techniques.

Animals↗

PubMedDate not supplied

Perilesional IL-2 treatment of a VX2 head-and-neck cancer model can induce a systemic anti-tumour activity.

BACKGROUND: Head-and-neck cancer is associated with impaired cell-mediated immune reactivity. A rabbit model with VX2 Squamous Cell Carcinoma transplanted into both auricles was used to test the effects of a regimen for local Interleukin 2 (IL-2) therapy, optimal in murine tumour models. MATERIALS AND METHODS: Peri-tumoural IL-2 treatment started when one of the tumours exceeded 2 cm2 and consisted of 100,000 or 300,000 Chiron Units IL-2 or only solvent during 5 consecutive days. RESULTS: In 4 out of 12 (33%) rabbits the treated primary tumours regressed completely, simultaneously with the non-treated contra-lateral tumours. Also metastases in draining lymph nodes of both treated and untreated primary tumours regressed in three of these animals. Tumour cells injected in the cured animals were rejected. The histology of the regressing tumours in cured cases showed an active granulomatous reaction with a histiocytic response, splitting up of tumour islands, and fibrinoid obstruction of blood vessels. CONCLUSION: These findings showed local and systemic therapeutic effects of this local IL-2 regimen in a VX2 head-and-neck cancer model.

Animals↗

PubMed1988

Relationship between estrogen receptor status in the primary tumor and its regional and distant metastases. An immunohistochemical study in human breast cancer.

Treatment of metastatic breast cancer based on the estrogen receptor content (ER) of the primary tumor builds on the assumption that the ER status of the primary tumor and the metastases are largely equal. Studies addressing this question have used ligand-binding assays for ER determination and have consequently been subject to the limitations of this technique. Reported disparity rates have been 20%. In order to avoid some of these limitations, we used an immunohistochemical assay in paraffin-embedded tissue. Among a total of 92 examined regional lymph node metastases, ER status was equal with that of their 37 primaries in 84 cases (91%). Semiquantified ER content was significantly correlated in primary tumor and the metastases (r = 0.67, p less than 0.001). Among a total of 51 distant metastases, equal ER status was found in 44 (86%) cases and a quantitative relationship could not be established. Disparities can be due to methodological errors in the histochemical assay or tumor heterogeneity.

Abdominal Neoplasms↗

PubMed1998

The use of percent free prostate specific antigen for staging clinically localized prostate cancer.

PURPOSE: The free-to-total serum prostate specific antigen (PSA) ratio (percent free PSA) has been demonstrated to have clinical use for early detection of men with prostate cancer with total PSA levels between 4.0 and 10.0 ng./ml. Several studies evaluating the usefulness of percent free PSA for the staging of clinically localized prostate cancer have provided conflicting results. We further investigate the usefulness of percent free PSA for staging of clinically localized prostate cancer. MATERIALS AND METHODS: In 263 men with clinically localized prostate cancer who underwent radical prostatectomy total PSA and free PSA were measured preoperatively. Pathological stages were classified as organ confined in 134 cases, capsular penetration in 92, seminal vesicle involvement in 7, involvement of the surgical margins in 20 and lymph node involvement in 10. RESULTS: Percent free PSA was significantly different between men with organ confined versus nonorgan confined tumors (p <0.0001) and between those with favorable versus unfavorable pathology (p <0.0001). A cutoff of 12% free PSA provided a 72% positive predictive value and 52% negative predictive value for favorable pathology. A cutoff of 15% free PSA provided a 76% and 53% positive and negative predictive value, respectively, for organ confined disease. CONCLUSIONS: These data demonstrate that the use of percent free PSA may be of additional value for the staging of clinically localized prostate cancer. The recommendations for cutoff levels of percent free PSA for detection and staging of localized prostate cancer are preliminary and can only be given for this particular assay. A large multicenter trial, controlling for age, stage and grade distribution, as well as for a uniform pathological evaluation and comparable total and free PSA assays, is required to elucidate this issue further.

Aged↗

PubMed1981

Pregnancy-induced alterations in graft-versus-host responsiveness of uterine-draining and peripheral lymph node cells toward fetal alloantigens.

The popliteal lymph node assay was used to assess the effects of allogeneic pregnancy on the graft-versus-host (GVH) responsiveness of maternal uterine-draining and peripheral lymph node cells toward fetal alloantigens. These two cell populations were obtained from three groups of female mice: BALB/c virgins, BALB/c females 13 days pregnant by C3H males, and BALB/c females 13 days pregnant by BALB/c males. Recipients of the donor cells were (BALB/c x C3H)F1 and (BALB/c x C57)F1 hybrids. Uterine-draining lymph node (UDLN) cells at day 13 of an allogeneic pregnancy were specifically hyporesponsive toward fetal alloantigens compared to peripheral lymph node cells from the same donors. There was no difference in responsiveness between uterine-draining and peripheral lymph node cells in virgin or syngeneically pregnant mice. Therefore, the local nodes draining the uteri of primigravid mice carrying allogeneic fetuses, but not syngeneic fetuses, showed a specific decrease in GVH activity toward fetal alloantigens.

Animals↗

PubMed2002

Conjunctival macrophage-mediated influence of the local and systemic immune response after corneal herpes simplex virus-1 infection.

Recently it has been shown that selective subconjunctival macrophage depletion reduced the incidence and severity of stromal herpes simplex virus (HSV) keratitis in mice. In this study, we examined the effect of conjunctival macrophage depletion on the corneal and systemic T-cell-mediated immune response. BALB/c mice were treated with subconjunctival injections of dichloromethylene diphosphonate (Cl2MDP)-liposomes (Cl2MDP-LIP) or phosphate-buffered saline (PBS) 7 and 2 days before corneal infection with 105 plaque-forming units (PFU) of HSV-1 (KOS strain). Interferon (IFN)-gamma, interleukin (IL)-2, and IL-4 production in the cornea was analysed by enzyme-linked immunosorbent assay (ELISA), and cytokine mRNA levels (IFN-gamma, IL-4) were measured by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Cell culture supernatants from submandibular lymph nodes were analysed by ELISA for expression of IFN-gamma, IL-2, and IL-4 and by bioassay for IL-6. The HSV-1-specific proliferative response of lymphocytes from regional lymph nodes and the delayed-type hypersensitivity (DTH) response were tested after corneal infection. Virus-neutralizing antibody titres and HSV-1-specific immunoglobulin G (IgG)2a/IgG1-ratios were measured. Cytokine mRNA expression (IFN-gamma, IL-4) and secretion (IFN-gamma, IL-2, IL-4) in the corneas were decreased after HSV-1 corneal infection in the macrophage-depleted mice. The secretion of IFN-gamma and IL-2 was decreased in the regional lymph nodes from Cl2MDP-LIP-treated animals (P<0.05). Furthermore, Cl2MDP-LIP-treated mice had decreased HSV-1 specific proliferative responses (P<0.05) and DTH response after corneal HSV-1 infection (P<0.05). The virus-neutralizing serum-antibody levels (P<0.05) increased while the HSV-1 specific IgG2a/IgG1-ratio was unaffected after macrophage depletion. Macrophage depletion did not induce a shift between the T helper 1 (Th1) and Th2 response in this HSK model. The data suggest that conjunctival macrophage functions are enhancing the T-cell-mediated immune response after corneal infection. This effect is at least in part responsible for the impaired course of herpetic keratitis after macrophage depletion.

Animals↗

PubMed1994

Serial serum CA 125 measurements for evaluation of recurrence in patients with endometrial carcinoma.

OBJECTIVE: To evaluate the usefulness of serum assays for CA 125 to detect recurrent endometrial carcinoma. METHODS: Two hundred sixty-six patients were studied with 1101 post-treatment assays. Patients were categorized as low, medium, or high risk based on surgical-pathologic findings. CA 125 values were analyzed with respect to each patient's disease status. RESULTS: Serial CA 125 levels were elevated (greater than 35 U/mL) in 19 of 33 patients (58%) with recurrent disease. Among 236 surgically treated patients, 97 (41.1%), 42 (17.8%), and 97 (41.1%) were considered low, medium, and high risk, respectively. None of the low-risk and only two (4.7%) of the medium-risk patients developed recurrent disease. One of the latter patients was detected based on an elevated CA 125 level alone. Twenty-seven (27.8%) of the high-risk patients developed recurrent disease, 23 of whom had elevated pre-treatment CA 125. Fifteen of 16 (94%) with recurrent disease had an elevated CA 125 level. Nine of 12 patients with papillary serous carcinoma experienced recurrence; eight of these nine had elevated CA 125 levels at diagnosis and recurrence, in contrast to only one patient with a normal pre-treatment level (P = .018). False elevations were noted in 13 patients, 12 of whom had received radiation therapy. CONCLUSIONS: CA 125, if elevated at diagnosis of endometrial carcinoma, is an important marker for recurrent disease. The use of serial CA 125 assays is most beneficial in diagnosing recurrence in a high-risk population, including patients with papillary serous carcinomas. False elevations may occur following radiation therapy.

Adenocarcinoma, Clear Cell↗

PubMed1995

Low incidence of mbr bcl-2/JH fusion genes in Hodgkin's disease.

Lymph node biopsies from 140 cases of Hodgkin's disease (HD) and from 30 non-malignant lesions were screened for the presence of t(14;18) translocations involving the major breakpoint region (mbr) of the bcl-2 gene and the joining region (JH) of the immunoglobulin heavy chain gene, using a polymerase chain reaction (PCR) assay with subsequent nucleotide sequencing of amplified bcl-2/JH junctional regions. Expression of the bcl-2 protein within the Hodgkin and Reed-Sternberg (HRS) cells was investigated in 86 cases of HD by immunohistochemistry on cryostat or paraffin sections. Although bcl-2 expression could be found in a proportion of neoplastic cells in up to one-third of HD cases, the frequency of t(14;18) gene fusions detected by PCR was low. We identified such gene fusions in only 3 out of 140 (2 per cent) HD cases, one biopsy of which presented with four clonally distinct bcl-2/JH sequences. No t(14;18) was found in any of 30 reactive lymph node lesions. All fusion gene sequences were unique regarding the localization of the chromosome 14 and 18 breakpoints and the extranucleotide N-insertions. None of these gene fusions conformed to t(14;18) breakpoint sequences previously characterized in our laboratories. Our findings point to a mere coincidence in some cases of HD lesions and cells carrying a t(14;18) in the same biopsy and argue against a significant role of bcl-2 in the pathogenesis of HD.

Base Sequence↗

PubMed1997

"PERFEXT": a direct method for quantitative assessment of cytokine production in vivo at the local level.

A method termed "PERFEXT", based on sequential perfusion and detergent extraction of lymphoid and non-lymphoid organs, has been developed for the quantitative measurement of cytokines produced at a local level in a given tissue. In vivo treatment of mice with Staphylococcus enterotoxin B (SEB) or lipopolysaccharide (LPS) served as the model systems. Interleukin-2 (IL2) and interferon-gamma (IFN gamma) levels were monitored by ELISA analysis of extracted samples. After local footpad (FP) injection with SEB, spleen and serum IL2 levels peaked at 2-4 h, while IL2 levels peaked at around 4-8 h in both FP and popliteal lymph nodes. SEB injection resulted in increased IFN gamma levels both in the FP and the draining lymph node. The detection of cytokines in the intestine allows for the application of the method at mucosal sites as well, provided enzyme inhibitors are present during the extraction procedure. After FP injection with LPS, IFN gamma production was significantly increased in the draining lymph node and was detectable in the FP, whereas IL2 was undetectable in any organ examined. IL2 and IFN gamma could also be detected at the site of elicitation of a delayed-type hypersensitivity reaction following local FP challenge. Local cytokine production correlated with the swelling response, whereas cytokine production in the spleen did not. IL2 peaked early, followed by a late increase in IFN gamma production, corresponding to the maximum swelling. This simple method should prove useful for analysing the production of other cytokines in vivo in distinct anatomical compartments.

Animals↗

PubMed2004

Detection of melanoma cells in the lymphatic drainage after lymph node dissection in melanoma patients by using two-marker reverse transcriptase-polymerase chain reaction assay.

BACKGROUND: The aim of this study was to evaluate the role of melanoma gene expression as a marker of the presence of melanoma cells in lymphatic drainage routinely collected after lymphadenectomy and to correlate reverse transcriptase-polymerase chain reaction (RT-PCR) assay results with recurrence, survival, and prognostic factors. METHODS: We collected 24-hour postoperative lymphatic drainage samples (between days 2 and 4) from 93 patients with stage III melanoma who underwent radical lymphadenectomy between May 2002 and November 2003. We used RT-PCR assays with primers specific for the tyrosinase and MART-1 (Melan-A) genes. The samples were considered positive if at least one marker was expressed. Median follow-up time was 12.8 months. RESULTS: In 18 (19.4%) of 93 patients, the RT-PCR assay results were positive: in 8 of 18 for tyrosinase only, in 7 of 18 for MART-1 only, and in 3 of 18 for both markers. We observed a significantly higher recurrence rate in patients with positive RT-PCR results (15 of 18; 83%) than negative results (26 of 75; 35%; P = .0001). Positive results of RT-PCR correlated with the number of involved lymph nodes (P = .0001) and extracapsular extension of nodal metastases (P = .03). We observed significant differences in overall and disease-free survival for RT-PCR-positive and -negative patients in univariate and multivariate analyses. CONCLUSIONS: We observed positive RT-PCR assay results for melanoma cells in the lymphatic drainages of approximately 20% of patients after lymphadenectomy. This correlated significantly with early recurrence and shorter survival. These results may suggest that the RT-PCR assay could be useful for routinely analyzing postoperatively collected lymphatic drainage in stage III melanoma patients and for predicting disease progression.

Adult↗

PubMed1990

The effect of radiation therapy combined with natural killer cells against spontaneous murine fibrosarcoma.

The effect of radiation therapy combined with lymphoid cells against spontaneous murine fibrosarcoma (FSa-II) was investigated both in vivo and in vitro. In the in vivo experiment, syngeneic C3H mice were divided into 3 groups. Animals in the first group were injected with 1 x 10(5) tumor cells into the right hind leg. Animals in the second and third groups were injected with 1 x 10(5) tumor cells mixed with 1 x 10(7) normal lymphoid cells (NLC) or effector lymphoid cells (ELC), respectively. ELC were obtained from spleen and lymph nodes of FSa-II-bearing mice and incubated in vitro for 40 hr to eliminate suppressor T cell function. NLC were obtained from normal mice and incubated in the same way. Irradiation was given using 137Cs unit 3 days after cell inoculation. 12 out of 14 mice (85.7%) inoculated with tumor cells mixed with NLC did not show any tumor growth at 60 Gy local irradiation. 12 out of 21 mice (57.1%) inoculated with tumor cells alone and 6 out of 10 (60%) with tumor cells mixed with ELC rejected tumors at the same radiation dose. This synergistic effect with NLC was not observed when NLC was inoculated after irradiation, indicating that lymphoid cells should be in contact with tumor cells before irradiation. In the 51Cr release assay, lymphoid cells obtained from whole body irradiated (WBI) mice showed 17.8% lysis without irradiation and 28.8% lysis at 5 Gy irradiation. Untreated NLC showed almost no cytotoxic effect at the same radiation dose. This synergistic effect disappeared when WBI lymphoid cells were treated with anti asialo GM1 and complement.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2006

Management of adenoid cystic carcinoma of minor salivary glands.

PURPOSE: Adenoid cystic carcinoma (ACC) is a rare malignant tumor originating from the salivary glands. The characteristic clinicopathologic features of this tumor are perineural spread, local recurrences, and distant metastases. Radical surgery combined with radiotherapy, as mentioned in the literature, is the best method of treatment. This clinical review article is intended to analyze the outcome of management of a group of 22 ACC patients, who were treated in our clinic. METHODS: Between 1985 and 2000, 22 patients with ACC of minor salivary glands were treated in the Clinic of Oral and Maxillofacial Surgery of the "G. Papanikolaou" General Hospital, in Thessaloniki. The age range was 22 to 87 years. The distribution of the primary sites was buccal mucosa (3), floor of the mouth (1), hard palate (3), soft palate (2), junction of hard and soft palate (7), and hard or soft palate with spread in the paranasal sinus etc (6). All the patients were treated radically with surgery. The surgery was combined with radiotherapy in 17 patients. A total dose of 60 Gy in a 30- to 40-day period was given, using conventional 2 Gy fractions per day. Immunohistochemical assay of the expression of the Ki-67 antigen was performed on a subset of 15 cases. RESULTS: The mean follow-up range was 4 to 14 years. From the 22 patients, 15 (68.18%) were alive for more than 5 years and 6 (27.7%) had died from the disease. Eight patients were free of the disease for more than 5 years (ranging from 7 to 14), 4 patients were free of the disease for 5 years, and 3 patients were free of the disease for 4 years. One patient lived more than 10 years and died from another cause. Local recurrence was developed in 2 patients. One recurrence occurred within the first year after the treatment and the second local recurrence occurred 13 years after the initial treatment. Lymph node metastases occurred in 2 patients, 3 years and 7 years after completing the treatment. Distant metastases (lung) occurred in 2 patients, 2 years and 6 years after completing the treatment. The Mann-Whitney statistical analysis was used for comparing the Ki-67 values in correlation with prognosis and location of ACCs. The Ki-67 value was significantly higher in tumors from patients with treatment failure than in nonfailures (P < .001). The Ki-67 expression was also higher in large tumors characterized by wide topical spread (P < .005). CONCLUSIONS: The most proper method of treatment for ACC seems to be radical resection combined with radiotherapy. The treatment failure is associated with positive margins of the excised surgical specimen and named nerve involvement. The immunohistochemical study of Ki-67 expression may provide additional prognostic information for this tumor.

Adult↗

PubMed2001

Comparative studies of the estrogen receptors beta and alpha and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma.

An antibody, GC-17, thoroughly characterized for its specificity for estrogen receptor-beta (ER-beta), was used to immunolocalize the receptor in histologically normal prostate, prostatic intraepithelial neoplasia, primary carcinomas, and in metastases to lymph nodes and bone. Comparisons were made between ER-beta, estrogen receptor-alpha (ER-alpha), and androgen receptor (AR) immunostaining in these tissues. Concurrently, transcript expression of the three steroid hormone receptors was studied by reverse transcriptase-polymerase chain reaction analysis on laser capture-microdissected samples of normal prostatic acini, dysplasias, and carcinomas. In Western blot analyses, GC-17 selectively identified a 63-kd protein expressed in normal and malignant prostatic epithelial cells as well as in normal testicular and prostatic tissues. This protein likely represents a posttranslationally modified form of the long-form ER-beta, which has a predicted size of 59 kd based on polypeptide length. In normal prostate, ER-beta immunostaining was predominately localized in the nuclei of basal cells and to a lesser extent stromal cells. ER-alpha staining was only present in stromal cell nuclei. AR immunostaining was variable in basal cells but strongly expressed in nuclei of secretory and stromal cells. Overall, prostatic carcinogenesis was characterized by a loss of ER-beta expression at the protein and transcript levels in high-grade dysplasias, its reappearance in grade 3 cancers, and its diminution/absence in grade 4/5 neoplasms. In contrast, AR was strongly expressed in all grades of dysplasia and carcinoma. Because ER-beta is thought to function as an inhibitor of prostatic growth, androgen action, presumably mediated by functional AR and unopposed by the beta receptor, may have provided a strong stimulus for aberrant cell growth. With the exception of a small subset of dysplasias in the central zone and a few carcinomas, ER-alpha-stained cells were not found in these lesions. The majority of bone and lymph node metastases contained cells that were immunostained for ER-beta. Expression of ER-beta in metastases may have been influenced by the local microenvironment in these tissues. In contrast, ER-alpha-stained cells were absent in bone metastases and rare in lymph nodes metastases. Irrespective of the site, AR-positive cells were found in all metastases. Based on our recent finding of anti-estrogen/ER-beta-mediated growth inhibition of prostate cancer cells in vitro, the presence of ER-beta in metastatic cells may have important implications for the treatment of late-stage disease.

Aged↗

PubMed1988

Anti-tumour efficacy of IL-1 and IL-2.

The potential value of RIL-1 and RIL-2 for local immunotherapy of cancer was compared in the experimental model of MC-induced sarcomas growing in syngeneic (B10) mice. Highly purified recombinant human RIL-1 (Hoffmann-La Roche) and RIL-2 (Amersham) were administered s.c. into the area of lymph nodes draining the growing tumour. Within the dose range examined, RIL-2 was capable of inducing inhibition of tumour growth or complete regression of tumours and the cure of the majority of treated mice. In contrast, RIL-1 could neither inhibit tumour growth nor potentiate the tumour-inhibitory effect of RIL-2.

Animals↗

PubMed1998

[Successful chemotherapy based on in vitro chemosensitivity testing in a case of recurrent thymic carcinoma].

A 71-year-old woman underwent radical resection in May 1994 for a mediastinal mass invading the anterior chest wall. Histopathological examination revealed adenosquamous cell carcinoma. She was treated with postoperative chemotherapy including 5-fluorouracil (5-FU) and 4'-D-tetrahydropyrayl-doxorubicin (THP), based on in vitro chemosensitivity testing (CST), by MTT assay, using a surgical specimen. In December 1994, a recurrent tumor was detected on the left anterior chest wall and the patient received two courses of 5-FU, THP and methotrexate (MTX). The size of the chest-wall tumor decreased 25%. In July 1995, the patient had involvement of the left axillary lymph node and brain metastases in addition to the mass on the chest wall. Therefore, cisplatin, 5-FU and MTX were selected as treatment agents, based on CST using a metastatic axillary lymph node. After two courses of these agents, chest computed tomography showed a 91% reduction in the size of the chest wall tumor. Radiation was administered for the brain metastasis. In March 1997, the patient died of thymic carcinoma.

Aged↗

PubMed2002

Axillary lymph node cellular immune response to HER-2/neu peptides in patients with carcinoma of the breast.

HER-2/neu peptides have recently been shown to induce a proliferative response by peripheral CD4(+) T cells in breast cancer patients. To investigate potential differences in the local cellular immune response between breast cancer patients with and without nodal metastases, lymphocytes were isolated from axillary lymph nodes from patients with breast cancer, and proliferative and cytokine responses to HER-2/neu peptides were determined. Freshly isolated lymphocytes from lymph nodes of 7 women undergoing surgery for invasive breast cancer were plated at 20 x 10(5) cells per well in triplicate. Cells were stimulated with HER-2/neu peptides at 50 microg/ml and with control antigens. Incorporation of tritium-labeled thymidine was determined 4 days later. The levels of the cytokines interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and IL-10 were determined at priming and at restimulation with HER-2/neu peptides using a cytokine-specific, double-sandwich, enzyme-linked immunosorbent assay (ELISA). Lymphocytes isolated from the axillary lymph nodes of the patients mounted significant cellular immune response to HER-2/neu peptides, manifested by proliferation and specific cytokine elaboration. Proliferative responses to HER-2/neu peptides were seen in lymphocytes of patients with and without overexpression of HER-2/neu in the primary tumor. In some patients, the proliferative response to HER-2/neu peptides in lymphocytes from lymph nodes with metastases was absent or blunted compared with the response in lymphocytes from lymph nodes without metastases from the same patient (p < 0.05). HER-2/neu peptides induced a predominantly T helper type 1 (Th1) pattern of cytokine response in nodal lymphocytes isolated from breast cancer patients. A Th1-specific cytokine production pattern was maintained at priming and restimulation with HER-2/neu peptides and was amplified with IL-12 costimulation. These results indicate that HER-2/neu peptides can activate T cells in draining lymph nodes from women with invasive breast cancer. This activation is associated with a predominantly Th1 cytokine response, which suggests that conditioning with HER-2/neu peptides may be of value in the development of breast cancer vaccines.

Antigens, Neoplasm↗

PubMed1992

Regional chemotherapy for bladder neoplasms using continuous intravesical infusion of doxorubicin: impact of concomitant administration of dimethyl sulfoxide on drug absorption and antitumor activity.

BACKGROUND: One objective of regional chemotherapy is to achieve the therapeutic drug levels in local tissues and primary nodal drainage fields, while minimizing systemic drug toxicity. The composition of the drug-delivery vehicle may influence local drug absorption and thereby modulate both tissue drug levels and systemic toxicity. PURPOSE: We evaluated the effect of dimethyl sulfoxide (DMSO) as a drug-delivery vehicle on regional and systemic levels of doxorubicin (DOX) and on the cytotoxicity of DOX following continuous intravesical administration in an invasive rat transitional cell bladder carcinoma model. METHODS: F344 rats received continuous intravesical DOX infusion for a 7-day period using a regional drug administration system. A constant dose of DOX was administered in one of three DMSO concentrations (0%, 10%, or 50%) to groups of animals (N = 20 per group). These concentrations corresponded to target urinary concentrations of 0%, 0.1%, and 0.5%, respectively. DOX levels in urine, serum, muscle, liver, bladder wall, and retroperitoneal lymph nodes were measured using a fluorescence assay on experimental days 0, 2, 4, 6, and 8 (N = four animals/group per day). In vitro assays evaluated the effect of DMSO concentration on the cytotoxicity of DOX against six transitional cell carcinoma cell lines. A final experiment on rats with established bladder tumors compared the cytoreductive effect of continuous intravesical infusion of DOX in 50% DMSO with that of DOX alone and with that in a sham-treated control group; there were 20 rats in each group. RESULTS: Mean and peak tissue and serum levels of DOX increased as a direct function of DMSO concentration. Compared with the results in controls, mean concentrations of DOX in the bladder were increased 7.1-fold and 12.1-fold in the groups given 10% and 50% DMSO, respectively. Average drug concentrations in the lymph nodes were increased 9.6-fold and 9.3-fold in the groups given 10% and 50% DMSO, respectively. In vitro, DMSO synergistically enhanced the cytotoxicity of DOX in two of the six cell lines studied. Solubilizing the test agent in 5% DMSO reduced the IC50 (drug concentration required to reduce cell viability to 50% of control values) to an average of 56% +/- 41% (+/- SD) of control values; 10% DMSO further decreased the average IC50 to 20% +/- 18% (+/- SD) of control values. The mean bladder tumor weight of animals treated with the combination of DOX and DMSO was 0.52 g. This compared with a mean tumor-bearing bladder weight of 2.69 g in the control group (P = .012) and 0.80 g in the group treated with DOX alone (P = .0544). CONCLUSIONS: These results suggest that the use of DMSO as a solvent vehicle for DOX improves drug absorption while simultaneously potentiating DOX cytotoxicity. The use of DMSO as a drug carrier merits further evaluation as a way of enhancing the efficacy of regional chemotherapy regimens.

Administration, Intravesical↗