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PubMed1997

Effect of recombinant alpha-interferon on pharmacokinetics, biodistribution, toxicity, and efficacy of 131I-labeled monoclonal antibody CC49 in breast cancer: a phase II trial.

Preclinical studies have demonstrated that recombinant IFN-alpha (rIFN-alpha) can enhance the tumor associated glycoprotein 72 (TAG-72) on tumors. To determine whether rIFN-alpha could enhance TAG-72 expression in vivo in patients, 15 women with breast cancer were randomized to receive daily injections of rIFN-alpha (3 x 10(6) units/m2 for 14 days) beginning on day 1 (group 1 = 7 patients) or on day 6 (group 2 = 8 patients). On day 3, all patients received a 10-20-mCi tracer dose of 131I-CC49, a high-affinity murine monoclonal antibody reactive against TAG-72, followed by a therapy dose of 60-75 mCi/m2 of 131I-CC49 on day 6. Whole body and single-photon emission computed tomography scans along with whole blood pharmacokinetics were performed following tracer and treatment phases. Hematological toxicity was considerable; reversible grade 3-4 neutropenia and thrombocytopenia was observed in 12 of 15 patients. Twelve of 14 patients tested developed human antimouse antibodies 3-6 weeks after treatment. For group 1 patients, whole blood residence time increased significantly between that predicted from the tracer doses and therapy doses (42.6 +/- 4.7 versus 51.5 +/- 4.8 h, respectively; P < 0.01). The calculated radiation absorbed dose to red marrow from therapy compared to tracer activity was also significantly higher for this group (1.25 +/- 0.35 versus 1. 07 +/- 0.26 cGy/mCi; P < 0.05). Treatment with rIFN-alpha was found to enhance TAG-72 expression in tumors from patients receiving rIFN-alpha (group 1) by 46 +/- 19% (P < 0.05) compared to only 1.3 +/- 0.95% in patients not initially receiving IFN (group 2). The uptake of CC49 in tumors was also significantly increased in rIFN-alpha-treated patients. One partial and two minor tumor responses were seen. In summary, rIFN-alpha treatment altered the pharmacokinetics and tumor uptake of 131I-CC49 in patients at the expense of increased toxicity.

Adult↗

PubMed2005

Catenin expression in T1/2 carcinomas of the floor of the mouth.

Reduction of the expression of catenin is a crucial step in the pathogenesis, progression and prognosis of many epithelial cancers including squamous cell carcinomas (SCCs). Catenin expression in oral carcinomas was evaluated in relation to clinico-pathological features in order to determine its value as a prognostic marker. Eighty-five patients with histologically proven T1/2 squamous cell carcinoma of the oral floor who underwent surgical treatment were eligible for the study. A tissue microarray consisting of multiple representative tissue cores of each carcinoma was composed. The expression levels of alpha, beta and gamma-catenins were determined immunohistologically. Correlation between clinical features and the expression of catenin proteins was evaluated statistically using Kaplan-Meier curves, log-rank tests and chi(2)-tests. Loss of alpha-catenin expression in carcinoma of the floor of the mouth correlated significantly with poor prognosis (P=0.05). Conversely, significantly reduced rates of lymph-node metastases were observed in alpha- and beta-catenin-positive T1 and T2 SCCs. Loss of gamma-catenin expression indicated a reduced survival rate in nodal-negative tumours (P=0.02). Catenin expression in carcinomas of the floor of the mouth seems to be a predictive parameter in the prognosis of T1 and T2 SSCs.

Adult↗

PubMed2000

Soft tissue sarcomas after radiation treatment for breast cancer. Three case studies and review of literature.

AIMS: By means of 3 cases with infield soft tissue carcinomas after radiotherapy for breast cancer, symptoms and therapy are described. Consequences for treatment planning and patient's information before radiotherapy for breast cancer are discussed. PATIENTS: Three of 1,025 patients with breast cancer irradiated from 1984 to 1997 suffered from infield secondary soft tissue sarcomas. The latency periods were 61, 49 and 59 months. Two patients had been treated with breast-conserving therapy (computerized planning, 50 Gy to reference point, 5 times 2 Gy/week, 5-MV photons), 1 patient received a local boost dose of 15 Gy (10-MeV electrons), patient 3 radiotherapy of the thoracic wall and regional lymph nodes after mastectomy using 12-MeV electrons (thoracic wall) and 5-MV photons (lymph node areas) to 50 Gy, 5 times 2 Gy/week. No adjuvant chemotherapy was given. All sarcomas were very extensive, all patients died from local progression and/or distant failure after 17, 13 and 12 months. RESULTS: The incidence of spontaneous sarcomas of the breast is about 0.06%, after operation and radiotherapy 0.09 to 0.45%. No correlations to radiotherapy technique and no risk factors were found. Radiation dose could play a role, but there are very sparse data about this. CONCLUSIONS: Secondary soft tissue sarcomas are very rare, but familiar complications of radiotherapy. Only early diagnosis leads to a chance for cure. Because of unclear correlations to the treatment parameters and rareness of this event, in our opinion no regular information to the patient receiving radiotherapy for breast cancer is mandatory.

Aged↗

PubMed2002

[Expression of matrix metaloproteinase and tissue inhibitors in ovarian tumors].

BACKGROUND & OBJECTIVE: Metalloproteinase(MMPs) is considered to be associated with the development of carcinoma, especially with the invasion and metastases of cancer. This study was designed to evaluate the relationship between the expression of MMP-2, MMP-9, and TIMP-2 and biological behavior of ovarian cancer. METHODS: The expression of MMP-2, MMP-9, and TIMP-2 in 128 patients with ovarian tumor was determined using immunohistochemical methods, and their relationship to many clinicopathological parameters was analyzed. RESULTS: Immunohistochemical studies revealed a diffuse granular distribution of MMP-2, MMP-9, and TIMP-2 in the cytoplasm of the carcinoma cells. The expression of MMP-2, MMP-9, and TIMP-2 was stronger in ovarian adenocarcinoma tissue than in ovarian benign tumor tissue (P < 0.01). MMP-2 and MMP-9 levels were found to be significantly higher in grade III-IV adenocarcinoma than in grade I-II adenocarcinoma (P < 0.01). MMP-2 and MMP-9 levels were significantly higher in G3 than in G1-2 tumors. Furthermore, the expression rate of MMP-2 and MMP-9 was higher in cases with lymph node metastases thanin those with non-lymph node metastasis. TIMP-2 expression was contrary to the expression of MMP-2 and MMP-9 on that three respects in ovarian carcinomas. CONCLUSION: The expression of MMP-2, MMP-9, and TIMP-2 correlate with tumor stage, poor differentiation, and lymphonodes metastases, which suggests that co-expression of MMP-2, MMP-9, and TIMP-2 within the same tumor seem to play an important role in the progression of ovarian cancer and could be useful prognostic markers for patients with ovarian carcinoma.

Adolescent↗

PubMed1998

Expression of the vascular endothelial growth factor C receptor VEGFR-3 in lymphatic endothelium of the skin and in vascular tumors.

It is difficult to identify lymph vessels in tissue sections by histochemical staining, and thus a specific marker for lymphatic endothelial cells would be more practical in histopathological diagnostics. Here we have applied a specific antigenic marker for lymphatic endothelial cells in the human skin, the vascular endothelial growth factor receptor-3 (VEGFR-3), and show that it identifies a distinct vessel population both in fetal and adult skin, which has properties of lymphatic vessels. The expression of VEGFR-3 was studied in normal human skin by in situ hybridization, iodinated ligand binding, and immunohistochemistry. A subset of developing vessels expressed the VEGFR-3 mRNA in fetal skin as shown by in situ hybridization and radioiodinated vascular endothelial growth factor (VEGF)-C bound selectively to a subset of vessels in adult skin that had morphological characteristics of lymphatic vessels. Monoclonal antibodies against the extracellular domain of VEGFR-3 stained specifically endothelial cells of dermal lymph vessels, in contrast to PAL-E antibodies, which stained only blood vessel endothelia. In addition, staining for VEGFR-3 was strongly positive in the endothelium of cutaneous lymphangiomatosis, but staining of endothelial cells in cutaneous hemangiomas was weaker. These results establish the utility of anti-VEGFR-3 antibodies in the identification of lymphovascular channels in the skin and in the differential diagnosis of skin lesions involving lymphatic or blood vascular endothelium.

Adult↗

PubMed1998

Ventriculosaccular lymphoepithelioma of the larynx: case report and literature review.

BACKGROUND: Lymphoepithelioma is a very rare neoplasm of the larynx. The authors have reviewed the available published literature on the subject and found eight studies on lymphoepithelioma. Lymphoepitheliomas derive from the epithelial and lymphatic tissues of the laryngeal ventricule. The rarity of the occurrence of lymphoepithelioma makes it difficult to define its clinical features and general treatment methods. METHODS: The authors present a description of a lymphoepithelioma located in the left laryngeal sacculus, extending into the pre-epiglottic space and infiltrating the epiglottis with an ulceration of its laryngeal surface. A total laryngectomy and a left radical neck dissection were performed. After surgery, radiotherapy treatment was applied to the left cervical and laryngeal areas. Two years after the initial radiotherapy, the patient died during palliative chemotherapy (for metastases). RESULTS: In patients with lymphoepithelioma of the larynx, the following can be observed: (1) bulging of the laryngeal ventricule, with or without ulceration of the laryngeal surface of the epiglottic mucosa; (2) early lymph node and remote matastases. CONCLUSIONS: In the early stages of lymphoepithelioma, radiotherapy is the method of choice. In advanced cases of lymphoepithelioma, radiotherapy supplements surgical treatment.

Carcinoma, Squamous Cell↗

PubMed2005

[Expression of KAI1, MRP-1, and FAK proteins in lung cancer detected by high-density tissue microarray].

BACKGROUND & OBJECTIVE: The genesis, development, invasion, and metastasis of tumor are closely correlate with alterations of multi-genes. At present, the roles of Kang-ai-1 (KAI1), motility-related protein-1 (MRP-1), and focal adhesion kinase (FAK) in lung cancer have seldom been reported. This study was designed to investigate the roles of KAI1, MRP-1, and FAK in tumorigenesis and development of lung cancer, and their values in diagnosis and predicting the prognosis of lung cancer. METHODS: The expression of KAI1, MRP-1, and FAK proteins in a high-density tissue microarray containing 240 spots were detected by SP immunohistochemistry. RESULTS: The positive rates of KAI1 and MRP-1 were significantly lower in primary lung cancer than in normal lung tissue (25.9% vs. 100%, 42.6% vs. 100%, P<0.05). The positive rate of FAK was significantly higher in primary lung cancer than in normal lung tissue (44.4% vs. 10.0%, P<0.05). The expression of KAI1, FAK, and MRP-1 in primary lung cancer had no correlation with age and gender of the patients, and macroscopic and histological type of tumor, but had correlations with tumor differentiation, clinical stage, and lymph node metastasis. In addition, the expression of MRP-1 had correlation with histological type of tumor; the positive rate of MRP-1 was significantly lower in small cell lung cancer than in non-small cell lung cancer (0 vs. 50.0%, P<0.05). KAI1 expression was negatively correlated to FAK expression (rs=-0.458, P<0.05); MRP-1 expression was positively correlated with KAI1 expression (rs=0.535, P<0.05), and negatively correlated with FAK expression (rs=-0.438, P<0.05). CONCLUSIONS: The abnormal expression of KAI1, MRP-1, and FAK proteins are related to invasion and metastasis of lung cancer. Combined detection of the 3 proteins may be useful in predicting the development and prognosis of lung cancer.

Adult↗

PubMed2005

Expression of RPIP9 (Rap2 interacting protein 9) is activated in breast carcinoma and correlates with a poor prognosis.

MDR1 is upregulated in many tumors. We have previously detected activation of the MDR1 upstream promoter in metastatic breast cancer cells. MDR1 overlaps with an uncharacterized gene transcribed from the opposite strand, coding for Rap2 interacting protein 9 (RPIP9). Rap2 belongs to the Ras superfamily of GTPases, whose role in breast cancer remains unknown. We developed sensitive methods for detecting and quantifying RPIP9 mRNA and used it to identify these transcripts in normal human tissues, 60 biopsies of primary breast carcinoma, in isolated epithelial cells both from the primary tumor and from associated lymph nodes, and from bone marrow biopsies of 74 breast cancer patients. RPIP9 is expressed at high levels in normal testis, brain and adrenal gland, and at very low levels in normal breast. Tumorigenic breast carcinoma cell lines expressed RPIP9, whereas MCF-10A and HBL-100 that do not form tumors in nude mice had undetectable levels of RPIP9 mRNA. RPIP9 was activated in a high proportion of breast carcinomas (61.6%; n = 60) and a significant correlation with metastatic lymph node invasion (N = 0-3 vs. N > 3, where N = number of lymph nodes invaded; p = 0.031) was found. RPIP9 mRNA could be detected in malignant epithelial cells isolated from the primary tumor and from metastasized lymph nodes as well as in the bone marrow of significantly more poor-prognosis (N > 3) than better-prognosis (N = 0-3) patients (p = 0.001). Therefore, activation of RPIP9 occurs during the malignant breast epithelial transformation and increases with progression toward an invasive phenotype.

Amino Acid Sequence↗

PubMed2006

Tissue and circulating immunoreactive protein for MMP-2 and TIMP-2 in head and neck squamous cell carcinoma--tissue immunoreactivity predicts aggressive clinical course.

Useful markers showing biological aggressiveness of head and neck squamous cell carcinoma (HNSCC) are needed to predict the outcome of the disease. MMP-2 is associated with aggressive behavior of several solid cancers. In this study, the clinical significance of tumor tissue and circulating immunoreactive proteins for MMP-2 and TIMP-2 was assessed in HNSCC. The study group consisted of 74 patients with HNSCC and 44 healthy controls. Expression of MMP-2 and TIMP-2 was examined in paraffin-embedded tumor sections by immunohistochemical methods using specific antibodies. The pretreatment serum levels of MMP-2, TIMP-2 and MMP-2:TIMP-2 complex were quantitatively measured by ELISA assay. The results were compared with the clinicopathological factors of the disease and the patients' outcome. Immunohistochemical overexpression of MMP-2 in tumor was found to be prognostic for shortened survival in HNSCC, the 5-year cumulative relapse-free survival being 42% in patients with high positivity for MMP-2 in tumor vs 61% in cases with a negative or only weakly MMP-2-positive tumor (P=0.045). Tissue MMP-2 positivity was also strongly connected with later lymph node or hematogenic relapses and associated to the cause-specific survival (P=0.055). Similarly, the 5-year cause-specific survival was significantly poorer in patients with extensive positive immunostaining for tumor TIMP-2 than in those with a TIMP-2-negative tumor (40 vs 64%, P=0.038). Patients with a TIMP-2-positive tumor also had an unfavorable 5-year relapse-free survival rate (43 vs 60%, respectively, P=0.071). Additionally, the overexpression of TIMP-2 was a powerful predictor of later lymph node or hematogenous metastases in HNSCC. Serum levels of MMP-2, TIMP-2 or MMP-2:TIMP-2 complex failed to associate with the clinical behavior of HNSCC in this material. The results of this study provide evidence that MMP-2 and TIMP-2 immunoreactive protein in tumor tissue of HNSCC patients, but not when assayed from preoperative serum samples, are prognostic in estimation of the aggressive clinical course of HNSCC.

Adult↗

PubMed2003

Usefulness of tissue polypeptide antigen in the follow-up of bladder cancer.

OBJECTIVES: To evaluate the sensitivity and specificity of serum tissue polypeptide antigen (TPA) as a tumor marker for monitoring tumor recurrence in a prospective Phase II study. METHODS: This study consisted of 421 subjects allocated to three groups: 241 patients treated for bladder cancer between 1991 and 1995, 126 subjects with a previous history of bladder tumor but with no recurrence at the time of study enrollment, and 54 healthy volunteers. Soluble TPA concentrations were measured by radioimmunoassay. RESULTS: On the basis of receiver operating characteristic plot analysis, the normal test threshold was set at 63 U/L. For bladder cancer detection, the TPA specificity was 73% and sensitivity was 45%. TPA levels correlated with tumor stage (P <0.01), histologic grade, nodal stage, and metastatic stage and with urinary cytology in univariate analysis. In the subsets of patients with a history of bladder cancer and normal TPA levels, 34.9% experienced a relapse compared with 37.5% of patients with elevated TPA levels (no statistically significant difference). Among the patients with normal TPA levels who experienced recurrence, the mean disease-free interval was 30.6 months compared with 25.1 months in patients with elevated TPA levels (no statistically significant difference). Multivariate analysis showed that TPA was not an independent prognostic biomarker for tumor relapse. CONCLUSIONS: In patients with bladder cancer, the TPA serum level correlated with initial tumor stage and grade, but it was not useful for detecting or monitoring relapses.

Biomarkers, Tumor↗

PubMedDate not supplied

Impact of preoperative CA 15-3 levels in operable breast cancer. Comparison with tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA).

CA 15-3, TPA and CEA were assayed before surgery in 60 patients with breast cancer. A significant association was found between preoperative CA 15-3 levels and some of the most important prognostic factors in breast cancer, such as lymph node status and tumor size. No similar association was discovered for CEA and TPA. Preoperative CA 15-3 levels were also significantly associated with early recurrences of the disease, thus adding useful information to prognosis especially in N+ patients.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1982

[Late results of the combined treatment of locally disseminated soft tissue sarcomas].

Radical surgery was performed in 69 cases of primary and recurrent localized soft-tissue sarcomas (extended dissection of tumor--53, exarticulation or amputation--16) after a course of non-uniform irradiation, when other methods of specific treatment had failed. Areas of exposed tumors were irradiated with focal doses of 90-120 Gy, screened areas--with 40-60 Gy. Radiation was delivered through a latticed diaphragm from the same field. Postoperative complications due to intensive irradiation and radiation injury were comparable to those involved in standard radiation procedures. A 5-year survival rate was 50% (primary tumor--16 and relapse--77%).

Adult↗

PubMed1986

[Lymph node topography and various features of the metastasis of malignant kidney tumors].

Due to investigations of 102 renal preparations performed on corpses of mature persons, topographic peculiarities of the lymph nodes, getting lymph from the left and right kidneys, are revealed. Every lymph node of the left kidney gets greater amount of lymphatic vessels than every node of the right kidney. The lymph, running from the right kidney, usually gets through a less number of the subsequently arranged nodes up to the thoracic duct, as compared to the lymph, that runs from the left kidney. A typical position for the node, which the renal lymphatic vessels get into, is the fatty tissue in the area of the angle formed by the aorta edge and the inferior wall of the corresponding renal artery. The lymphatic nodes of the right kidney are arranged in the fatty tissue more compact than the left ones. These peculiarities, revealed by morphological investigations, are proved by analysis of 114 case histories of persons suffering from malignant neoplasms in the kidneys.

Adult↗

PubMed2002

Correlation of tissue inhibitor of metalloproteinase-2 with proliferative activity and patients' survival in breast cancer.

Tissue inhibitors of metalloproteinases (TIMPs) are endogenous regulators of matrix metalloproteinases (MMPs). They are believed to possess several distinct cellular functions, particularly the contradictory activities of inhibiting MMPs and promoting tumor cell growth. Immunohistochemistry was performed to detect TIMP-2 protein in 136 infiltrative breast carcinomas. TIMP-2 protein was analyzed in parallel with clinicopathologic features (tumor size, histologic type, nuclear and histologic grade, stage), patients' overall survival and ER, PR, Ki-67, topo IIalpha, c-erbB-2, p53 and bcl-2 proteins. Statistical analysis was performed using univariate and multivariate models analysis. Immunoreactivity for TIMP-2 was observed in cancer cells and stromal fibroblasts in 106 (77.94%) and 104 (76.47%) of 136 cases, respectively. TIMP-2 protein expression in stromal fibroblasts showed a statistically significant inverse correlation with tumor size (P =.014). An inverse correlation was also observed between TIMP-2 epithelial immunoreactivity and nuclear and histologic grade (P =.036 and P =.007, respectively). TIMP-2 protein reactivity showed statistically significant positive associations with topo IIalpha and bcl-2 in stromal and cancer cells, respectively (P =.032 and P =.001, respectively). TIMP-2 protein expression in cancer and stromal cells was associated with better patients' overall survival (P =.002 and P =.038, respectively). When evaluated by the Cox's proportional hazard regression model, this association was further established, but only as far as TIMP-2 expression in tumor epithelium was concerned (P =.019). Our results support the multifunctional potential of TIMP-2 through its correlation on the one hand to a favorable outcome, due to its MMP inhibitory activity and on the other to topo IIalpha contributing to its growth factor activity.

Adult↗

PubMed1992

[Malignant tumors of the head and neck in children. Part I--review].

About 27% of malignant tumors in children is located in the head and neck. Besides primary solid tumors, lymph node metastases as well as signs of systemic diseases of the lymphatic tissue are often found in this region. The latter are the most common childhood malignancies. Among primary solid malignant tumors in this region neoplasms of the soft tissues are frequency found. Their prevalence comes next to the tumors of the central nervous system and the orbit. Rhabdomyosarcoma (RMS) represents 50% of cases in this group. Malignant neoplasms originating from epithelial and bone tissue occur rarely in children. The evolution of triple therapy, combining surgery with irradiation and chemotherapy has produced and improvement in prolonged survival rates in these children.

Child↗

PubMed2026

CD44 gene rs9666607 polymorphism is associated with papillary thyroid carcinoma and interacts with CREB3L1.

BACKGROUND: The incidence of papillary thyroid carcinoma (PTC) has been rising. CD44 is involved in cell adhesion and migration, but the role of its genetic variation in PTC remains unclear. METHODS: This study aimed to investigate the association of CD44 gene polymorphisms with PTC and to examine the interaction between CD44 and CREB3L1. This study enrolled 354 patients with PTC, and the genotype distribution of the CD44 polymorphism (rs9666607) was analyzed. Key PTC genes were screened using the Gene Expression Omnibus (GEO) database (GSE33630). Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on these key genes. CD44 expression was validated using TCGA database, ELISA, qRTPCR, Western blot, and IHC in patient tissues, PTC mouse model, and human cell lines. The direct interactive molecules were screened through a bioinformatics method. RESULTS: The GSE33630 dataset identified a total of 124 upregulated and 85 downregulated differentially expressed genes. Enrichment analysis revealed 12 key PTC genes, including CD44. TCGA database validation revealed that CD44 was significantly overexpressed in PTC patients. The rs9666607‑A allele was associated with an increased risk of PTC and lymph node metastasis under a dominant model. CD44 mRNA and protein levels were significantly higher in PTC tissues versus adjacent tissue and further elevated in metastatic cases. Bioinformatic analysis predicted CD44 interaction with the transcription factor CREB3L1, and this was confirmed by molecular docking. CREB3L1 expression was synchronously upregulated with CD44 in PTC. CONCLUSION: CD44 polymorphisms, particularly the rs9666607-A allele, are significantly associated with PTC risk and metastasis in the studied population. CD44 is overexpressed in PTC, and its interaction with CREB3L1 suggests a potential novel interaction in PTC pathogenesis.

Hyaluronan Receptors↗

PubMed1998

Metastatic RCC arising in a transplant kidney.

We report a case of metastatic renal cell carcinoma arising in a cadaver transplant kidney 6 years after transplantation. Due to molecular analysis of the tumor tissue we could prove that the carcinoma originated from the male donor. After tumor resection and interruption of immunotherapy, the concomitant bone and lymph node metastases resolved with alpha-interferon and interleukin-2-based immunotherapy.

Antineoplastic Agents↗

PubMed1980

[Ectopic lacrimal gland under the bulbar conjunctiva].

In a 20-year-old female patient a small tumor (3 mm in diameter) was found in the upper nasal quadrant of the left conjunctiva bulbi. Lymphangiography showed that the conjunctival lymph vessels were ectatic. The histological study identified the excised material as tissue of the lacrimal gland.

Adult↗