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At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Improved sensitivity in the diagnosis of gastro-intestinal tumors by fuzzy logic-based tumor marker profiles including the tumor M2-PK.

The aim of this study was to improve diagnostic efficiency in the detection of gastro-intestinal cancers by using fuzzy logic modeling in combination with a tumor marker panel (CEA, CA72-4, CA19-9) including Tumor M2-PK. In this prospective study histologically confirmed colorectal (n=247), esophageal (n=86) and gastric cancer (n=122) patients were investigated and compared to control (n=53) persons without any malignant diseases. Tumor M2-PK was measured in plasma with an ELISA (ScheBoBiotech, Germany); all other markers were measured in sera (Roche, Germany). At 95% specificity, tumor detection was possible by the best single marker in colorectal cancer patients in 48% (Tumor M2-PK), in gastric cancers in 61% (CA72-4) and in esophageal cancers in 56% (Tumor M2-PK). A fuzzy logic rule-based system employing a tumor marker panel increased sensitivity significantly in colorectal cancers (p<0. 001) to 63% (Tumor M2-PK and CEA), in gastric cancers (p<0.001) to 81% (Tumor M2-PK and CA 72-4) and in esophageal cancers (p<0.02) to 74% (Tumor M2-PK and CA72-4). Adding a third marker further improved the sensitivity only marginally. Fuzzy logic analysis has proven to be more powerful than measurement of single markers alone or combinations using multiple logistic regression analysis of the markers. Therefore, with the fuzzy logic method and a tumor marker panel (including Tumor M2-PK), a new diagnostic tool for the detection of gastro-intestinal cancers is available.

Aged↗
PubMed1997

Primary germ cell tumors of the mediastinum: III. Yolk sac tumor, embryonal carcinoma, choriocarcinoma, and combined nonteratomatous germ cell tumors of the mediastinum--a clinicopathologic and immunohistochemical study of 64 cases.

BACKGROUND: Yolk sac tumor (YST), embryonal carcinoma (EC), choriocarcinoma (CC), and combined germ cell tumors (CGCTs) of the mediastinum are uncommon neoplasms. Only sporadic cases have been documented in the literature; therefore, the clinical behavior of these tumors when located in the mediastinum remains relatively unknown. METHODS: The clinical and pathologic features of 64 cases of primary YST, EC, CC, and CGCTs without teratomatous components were reviewed. The immunohistochemical findings in 29 cases were also analyzed using a panel of monoclonal and polyclonal antibodies in formalin fixed, paraffin embedded tissues. RESULTS: The patients were all men between the ages of 14 and 63 years (mean, 38.5 years). Their clinical symptoms included chest pain, shortness of breath, chills, fever, and superior vena cava syndrome. None of the patients had a previous history of testicular neoplasm or tumor elsewhere. Macroscopically, the lesions in 27 patients were described as large, soft, hemorrhagic, and in some cases necrotic, and varied in greatest dimension from 6 to 20 cm. Histologically, the tumors displayed morphologic features similar to those of their gonadal counterparts. Pure YSTs accounted for the majority of cases in this series (38 of 64, 60%), followed by pure CCs (8 of 64, 12%) and pure ECs (6 of 64, 9%). CGCTs accounted for only 18% of the total cases (12 of 64). YSTs showed a variety of growth patterns; however, the reticular pattern was the most commonly observed. ECs showed a more solid growth pattern with marked pleomorphism of the tumor cells and abundant areas of necrosis. CCs were characterized by the presence of cytotrophoblastic and syncytiotrophoblastic elements with frequent areas of necrosis and hemorrhage. The cases of nonteratomatous CGCT consisted of 5 cases of EC + YST, 2 cases of EC + seminoma, 4 cases of YST + seminoma, and 1 case of EC + CC. In clinical staging, 14 patients were Stage I, 6 were Stage II, and 19 were Stage III. Information on follow-up ranging from 1 month to 13 years was available for 40 patients. Seventeen patients with YST died of their tumors. Of these, 10 who presented with Stage III disease died within the first 2 years. Unfortunately, no clinical staging was obtained for the other 7 patients in this group, and they died within 6-36 months. It is noteworthy that 4 patients with YST have survived for more than 2 years; these patients presented in Stages I and II, and 2 of them received aggressive therapy with chemotherapeutic agents and radiation. Two patients with Stage III EC died within 2 years. The remaining 4 patients with EC were lost to follow-up. Eight patients with CC died within 6 months after initial diagnosis; 7 of them presented Stage III disease and only 1 presented with Stage I. In the nonteratomatous CGCT category, 2 patients with EC + YST died within 2 years after initial diagnosis, whereas 3 patients with YST + seminoma were alive after 4-9 years. CONCLUSIONS: The results of this study confirm the aggressive nature of primary nonseminomatous germ cell tumor of the mediastinum; 72% of the patients with adequate follow-up died of their tumors within 6-36 months after diagnosis, despite aggressive therapy. Clinical and pathologic staging of mediastinal YST, EC, and CGCT are important parameters that may be helpful in predicting the clinical outcomes of patients with these tumors. The authors' findings suggest that the majority of tumors that are not limited to the mediastinum at the time of diagnosis have more aggressive behavior. On the other hand, mediastinal choriocarcinomas appeared to follow a very aggressive clinical course, regardless of treatment modality or clinical tumor stage.

Adolescent↗
PubMed2004

Tumor sensitivity to IFN-gamma is required for successful antigen-specific immunotherapy of a transplantable mouse tumor model for HPV-transformed tumors.

PURPOSE: Many human tumors lose responsiveness to IFN-gamma, providing a possible mechanism for the tumor to avoid immune recognition and destruction. Here we investigate the importance of tumor responsiveness to IFN-gamma in the successful immunotherapy of TC1 tumors that were immortalized with human papillomavirus proteins E6 and E7. METHODS: To investigate the role of IFN-gamma in vivo, we constructed a variant of TC1, TC1.mugR, that is unresponsive to IFN-gamma due to overexpression of a dominant negative IFN-gamma receptor. RESULTS: Using recombinant Listeria monocytogenes that express HPV-16 E7 (Lm-LLO-E7) to stimulate an antitumor response, we demonstrate that sensitivity to IFN-gamma is required for therapeutic efficacy in that Lm-LLO-E7 induces regression of TC1 tumors but not TC1.mugR. In addition, we show that tumor sensitivity to IFN-gamma is not required for inhibition of tumor angiogenesis by Lm-LLO-E7 or for trafficking of CD4+ and CD8+ T cells to the tumor. However, it is required for penetration of lymphocytes into the tumor mass in vivo. CONCLUSIONS: Our findings identify a role for IFN-gamma in immunity to TC1 tumors and show that loss of tumor responsiveness to IFN-gamma poses a challenge to antigen-based immunotherapy.

Animals↗
PubMed1998

Photosensitizing effects of m-tetrahydroxyphenylchlorin on human tumor xenografts: correlation with sensitizer uptake, tumor doubling time and tumor histology.

The photodynamic effects of m-tetrahydroxyphenylchlorin (mTHPC) were assessed on human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts grown in nude mice and were correlated with mTHPC uptake, histology and doubling time of the tumors. Non-thermal laser light was delivered to the tumor as surface radiation 4 days after intraperitoneal administration of 0.1 and 0.3 mg mTHPC/kg body weight, respectively. The extent of tumor necrosis was measured by histomorphometry. The mTHPC concentration in non-irradiated tumors was assessed by high-performance liquid chromatography (HPLC). The tumors were graded according to their doubling time and their vascular architecture as assessed by histology. The 0.1 mg/kg dose of mTHPC resulted in an equal uptake for all 3 tumor types but revealed a larger extent of photosensitized necrosis for adenocarcinoma, which displayed a delicate tumor stroma with numerous small capillary vessels, than for mesothelioma and squamous cell carcinoma, which were both poor in stroma and vessels. The 0.3 mg/kg dose of mTHPC resulted in a 2-fold higher tumor uptake for all 3 tumor types and in a larger extent of necrosis for mesothelioma and squamous cell carcinoma, but not for adenocarcinoma xenografts, compared with the lower drug dose. Our results demonstrate that different tumor xenografts respond differently to mTHPC-PDT for a given drug-light condition. In this setting, the photosensitizing effect was more closely related to the vascular architecture of the tumors than to the sensitizer uptake and doubling time of the different tumors

Adenocarcinoma↗
PubMed1978

Immune responses to weakly immunogenic virally induced tumors. I. Overcoming low responsiveness by priming mice with a syngeneic in vitro tumor line or allogeneic cross-reactive tumor.

This report describes model systems which show low primary in vitro syngeneic cytotoxic responses to a Moloney-induced YAC tumor (syngeneic in A mice) and a Rauscher-induced RBL5 tumor (syngeneic in C57BL/6 mice) and examines different approaches to overcome these defects. Two major findings were obtained: (a) spleen cells from A mice, injected with tumor cells from an in vitro tumor line YAC-1, derived from YACL, could generate a significant syngeneic cytotoxic response. In contrast, spleen cells from A mice injected with tumor cells from the in vivo tumor line failed to generate a syngeneic cytotoxic response. Thus, tumor cells from the in vitro line were more immunogeneic that those from the in vivo line. (b) Spleen cells from A mice which were injected with the cross-reactive allogeneic tumor RBL5, could generate significant cytotoxic responses to the syngeneic tumors YAC and YAC-1. Similarly, spleen cells from C57BL/6 mice injected with the cross-reactive allogeneic tumor YAC-1, could generate a significant cytotoxic response to the syngeneic tumor RBL5. Thus, cross-reactive allogeneic tumors could stimulate syngeneic cytotoxicity. The theoretical and the practical implications of these studies are discussed.

Animals↗
PubMed1991

The epidemiology of headache among children with brain tumor. Headache in children with brain tumors. The Childhood Brain Tumor Consortium.

In this report we present aspects of the epidemiology of headache (i.e., pain in the head, face, ear, or neck) among children with brain tumors. The data are derived from the 3,291 subjects in the Childhood Brain Tumor Consortium databank. Overall, 62% of the children with brain tumors experienced chronic or frequent headaches prior to their first hospitalization: 58% of children with supratentorial tumors and 70% of children with infratentorial tumors. The relative frequency of headache increased through age 7 and then leveled off regardless of tumor location. For children under age 5, headache rarely had a duration of more than 1 year prior to hospitalization. Among children over age 4, headache duration of at least one year was significantly greater for supratentorial than for infratentorial tumors. Children with a brain tumor and headache had a different distribution of symptoms and neurologic signs than those without headache. Tumor location and headache status were interactively associated with the presence of other symptoms and neurologic signs. Children with headache had a greater number of other symptoms and neurologic signs. Regardless of tumor location among children with headache, nausea or vomiting, papilledema, and hypoactive tendon reflexes were more frequent, while upper extremity weakness, optic atrophy, and irritability were less frequent. Diplopia, coma, stiff neck, anesthesia or hypesthesia, pupillary abnormalities, and abnormalities of personality, academic performance, or speech were associated with headache in children with supratentorial tumors. No specific symptoms or neurologic signs were associated with headache in children with infratentorial tumors. Supratentorial craniopharyngioma, ependymoma, and protoplasmic astrocytoma were associated with significantly high rates of headache as was infratentorial pilocytic astrocytoma.

Adolescent↗
PubMed1995

The tumor volume and clonogen number relationship: tumor control predictions based upon tumor volume estimates derived from computed tomography.

PURPOSE: While tumor volume is an important parameter predicting clinical outcome, its relationship to clonogen number remains uncertain. This uncertainty is related to many factors, among them treatment response heterogeneity, which obscures the influence of patients and treatment-related parameters. In this study, we analyze the effect of tumor volume on local and regional recurrence in a setting tightly controlled for dose, treatment time, and patient selection. The hypothesis that changes in clonogen number scale directly with changes in tumor volume is tested. METHODS AND MATERIALS: Using digital reconstruction of diagnostic computed tomography (CT) scans, primary and total tumor volumes were estimated in 51 cases of advanced squamous cell carcinoma of the head and neck. All patients were managed with a concomitant boost accelerated superfractionated schedule to a median dose of 70.2 Gy. Clinical data were fitted to a mixture model to relate tumor volume parameters to control probability where volume and clonogen number were related by the relationship m = a.Vb, where m is initial clonogen number, a is a proportionality constant, V is tumor volume, and b is the volume exponent. RESULTS: Tumor volume estimates for primary tumor ranged from 3-196 cm3 and for total tumor volume 5-196 cm3. Actuarial local-regional control is 63%. The estimated volume exponent b is 0.85 (95%, confidence interval (c.i.): 0.40-1.29) for primary tumor volume and 1.1 (95%, c.i.: 0.33-1.85) for total tumor volume. CONCLUSION: This study quantifies the adverse influence of tumor volume on local-regional disease control in advanced head and neck cancer. The derived volume exponent approximates to one, the theoretical expectation if the growth fraction is roughly constant and clonogen number increases linearly with volume. Finally, these results suggest that radiobiological parameters are more reliably estimated from clinical data with narrowly defined strata.

Carcinoma, Squamous Cell↗
PubMed1984

Tumor-to-tumor variability in the hypoxic fractions of experimental rodent tumors.

Paired determinations of the radiation responses of normally-aerated and artificially hypoxic rodent tumors, performed to measure the hypoxic fractions of the tumors, were obtained from our own laboratories and from the literature. The data were reanalyzed to assess whether the variabilities in the radiation responses of the normally-aerated and artificially hypoxic tumors were similar. If there were large differences in the hypoxic fractions of individual tumors within the experiments, the variability in the data from aerobic tumors would be expected to be greater than the variability in the data from artificially hypoxic tumors (which should all be brought to uniform hypoxia and therefore uniform radioresistance). The analyses revealed the variability to be as great or greater for hypoxic tumors as for normally-aerated tumors. This finding suggests that factors other than tumor-to-tumor differences in oxygenation produce most of the variability in the radiation responses of individual tumors from an experimental tumor line.

Animals↗
PubMed2003

Venezuelan equine encephalitis replicon immunization overcomes intrinsic tolerance and elicits effective anti-tumor immunity to the 'self' tumor-associated antigen, neu in a rat mammary tumor model.

Many tumor-associated antigens (TAAs) represent 'self' antigens and as such, are subject to the constraints of immunologic tolerance. There are significant barriers to eliciting anti-tumor immune responses of sufficient magnitude. We have taken advantage of a Venezuelan equine encephalitis-derived alphavirus replicon vector system with documented in vivo tropism for immune system dendritic cells. We have overcome the intrinsic tolerance to the 'self' TAA rat neu and elicited an effective anti-tumor immune response using this alphavirus replicon vector system and a designed target antigen in a rigorous rat mammary tumor model. We have demonstrated the capacity to generate 50% protection in tumor challenge experiments (p = 0.004) and we have confirmed the establishment of immunologic memory by both second tumor challenge and Winn Assay (p = 0.009). Minor antibody responses were identified and supported the establishment of T helper type 1 (Th1) anti-tumor immune responses by isotype. Animals surviving in excess of 300 days with established effective anti-tumor immunity showed no signs of autoimmune phenomena. Together these experiments support the establishment of T lymphocyte dependent, Th1-biased anti-tumor immune responses to a non-mutated 'self' TAA in an aggressive tumor model. Importantly, this tumor model is subject to the constraints of immunologic tolerance present in animals with normal developmental, temporal, and anatomical expression of a non-mutated TAA. These data support the continued development and potential clinical application of this alphaviral replicon vector system and the use of appropriately designed target antigen sequences for anti-tumor immunotherapy.

Amino Acid Sequence↗
PubMed1980

Endodermal sinus tumor (yolk sac tumor), seminoma and hemangiopericytoma. Rare primary mediastinal tumors. A report on the course of the disease in nine patients.

The pathological and clinical features of primary mediastinal hemangiopericytoma, seminoma, and endodermal sinus tumor are presented and discussed. These tumors were found in 3 patients each out of 898 cases of mediastinal tumor. Primary thoracic hemagiopericytomas are rare. The diagnosis can be determined by histology only, but nothing can be said about the malignancy of the tumor. Tumor recurrence is relatively frequent. Two patients were radically operated, and they are living today 4 and 4 1/2 years later, without evidence of recurrence. The third patient with clinically clearly malignant hemangiopericytoma was inoperable. This patient died 6 months after diagnosis. The anterior mediastinum is a predilection site for extragonadal germ cell tumors. Histologically there is no difference between this tumor and the gonadal seminoma. This tumor is well known to be radiosensitive. All 3 male patients were inoperable and received radiotherapy. One patient died after 4 months, the other 2 are living one and 3 years later, respectively, without complaints or evidence of recurrence. Only 12 cases of primary mediastinal endodermal sinus tumors have been reported in the literature, we observed 3 more such tumors. The highly malignant alpha-fetoprotein producing tumor occurs exclusively in young males. There is, as yet, no clear-cut form of treatment. One of our patients died after 2 weeks, another received chemotherapy and died a few months after diagnosis, the third received chemotherapy and irradiation and is living today, 20 months after discovery of the tumor.

Adult↗
PubMed1992

Ovarian serous tumors of low malignant potential (serous borderline tumors). The relationship of exophytic surface tumor to peritoneal "implants".

A series of 98 ovarian serous tumors of low malignant potential (LMP) was studied to test the validity of the implantation theory of extraovarian peritoneal spread of tumor by assessing the association between exophytic tumor on the ovarian surface and synchronous peritoneal implants. Patient's ages ranged from 17 to 77 years (mean, 37.8 years). The ovarian tumors were bilateral in 39 cases (40%). Exophytic tumor was present in 47 (48%) cases and involved at least one ovary in 82% of bilateral tumors. Exophytic tumor was found in 29 of 31 patients (94%) with peritoneal implants, but in only 18 of 67 patients (27%) without peritoneal implants. Moreover, 29 of 47 patients (62%) with exophytic tumor had peritoneal implants compared with only 2 of 51 patients (4%) without exophytic tumor. The utility of exophytic tumor as a marker of synchronous peritoneal implants had a diagnostic sensitivity of 94%, a diagnostic specificity of 73%, and an efficiency of 80%. Because of the strongly positive correlation between exophytic tumor and peritoneal implants, the implantation theory remains as a highly likely explanation for extraovarian spread of ovarian serous LMP tumors. The multicentric "field effect" theory, however, cannot be entirely excluded and may be operative in some cases.

Adolescent↗
PubMed2003

Percutaneous tumor ablation: reduced tumor growth with combined radio-frequency ablation and liposomal doxorubicin in a rat breast tumor model.

PURPOSE: To determine whether combined intravenous liposomal doxorubicin and radio-frequency (RF) ablation decreases tumor growth and increases endpoint survival over those with RF or liposomal doxorubicin alone in an animal tumor model. MATERIALS AND METHODS: Subcutaneous R3230 mammary adenocarcinoma (1.1-1.4 cm) was implanted in female Fischer rats. Initially, 35 tumors were randomized into four experimental groups: (a) conventional monopolar RF (70 degrees C for 5 minutes) alone, (b) liposomal doxorubicin (1 mg) alone, (c) RF ablation followed by liposomal doxorubicin, and (d) no treatment. Ten additional tumors were randomized into two groups that received a 90 degrees C RF dose either with or without liposomal doxorubicin. Tumor growth rates and the defined survival endpoint, the time at which the tumor reached 3.0 cm in diameter, were recorded. The effect of treatments on endpoint survival and tumor doubling time were analyzed by means of the Kaplan-Meier method and analysis of variance statistics. RESULTS: Differences in endpoint survival and tumor doubling time in the six groups were highly significant (P <.001). Endpoint survivals were 9.1 days +/- 2.5 for the control group, 16 days +/- 3.7 for tumors treated with 70 degrees C RF alone, 16.5 days +/- 3.2 for tumors treated with liposomal doxorubicin alone, and 26.6 +/- 5.3 days with combined treatment. For 90 degrees C RF ablation, endpoint survivals were 16.6 days +/- 1.2 and 31.5 days +/- 3.0 without and with liposomal doxorubicin (P <.01). Mean endpoint survival and tumor doubling times for the three RF levels (0, 70 degrees C, and 90 degrees C) were all significantly different (P =.01). Additionally, animals that received combined liposomal doxorubicin and 90 degrees C RF ablation survived longer than did animals that received combined liposomal doxorubicin and 70 degrees C RF ablation (P <.01). CONCLUSION: Combined RF ablation and liposomal doxorubicin retards tumor growth and may increase animal survival compared with that with either therapy alone or no therapy.

Animals↗
PubMed1995

Interstitial fluid pressure in human melanoma xenografts. Relationship to fractional tumor water content, tumor size, and tumor volume-doubling time.

The interstitial fluid pressure (IFP) has been shown to be elevated in malignant tissue, but the possibility that IFP might be related to other pathophysiological parameters of the tissue has not been fully explored. The purpose of the study here reported was to measure the IFP in human melanoma xenografts and to search for possible correlations between tumor IFP and fractional tumor water content, tumor wet weight, or tumor volume-doubling time. Tumors of four melanoma lines (A-07, D-12, R-18, U-25), grown orthotopically in BALB/c-nu/nu mice, were included in the study. Tumor IFP, measured by using the wick-in-needle technique, ranged from 2 to 10 mm Hg (D-12), from 2 to 15 mm Hg (A-07 and U-25), and from 2 to 30 mm Hg (R-18). Statistically significant correlations between tumor IFP on the one hand and fractional tumor water content, tumor wet weight, or tumor volume-doubling time on the other were not found, whether the tumor lines were analyzed individually or together. These observations suggest that simple general relationships between the IFP and the other pathophysiological parameters measured here, might not exist in tumors.

Animals↗
PubMed1994

Rhabdoid tumor of the kidney with primitive neuroectodermal tumor of the central nervous system: associated tumors with different histologic, cytogenetic, and molecular findings.

Rhabdoid tumor of the kidney (RTK) is associated with tumors of the central nervous system (CNS) in approximately 15% of cases. We describe the clinical features, histologic and cytogenetic findings, and molecular analysis of renal and CNS tumors from the same patient. The histology of the renal tumor was consistent with rhabdoid tumor. The CNS tumor was a primitive neuroectodermal tumor (PNET). The karyotype of the RTK was normal male. The PNET of the brain demonstrated monosomy 22 as the only cytogenetic abnormality, similar to reported cases of malignant rhabdoid tumor of the brain, but dissimilar to nonrandom cytogenetic findings in other CNS PNETs. Molecular cytogenetic and DNA marker studies confirmed loss of chromosome 22 in this patient's brain tumor. DNA allelotyping showed retention of both parental chromosome 22 alleles in the RTK and loss of the maternal allele in the PNET. Evaluation of additional RTKs and brain tumors occurring in the same patient may provide insight into the origins and relationships of these enigmatic tumors.

Brain Neoplasms↗
PubMed2003

Influence of radiation therapy delay on abdominal tumor recurrence in patients with favorable histology Wilms' tumor treated on NWTS-3 and NWTS-4: a report from the National Wilms' Tumor Study Group.

PURPOSE: This study was undertaken to determine whether radiation therapy (RT) delay of >or=10 days had an adverse impact on abdominal tumor recurrence among children with favorable histology (FH) Wilms' tumor enrolled in National Wilms' Tumor Study (NWTS) 3 and 4. METHODS AND MATERIALS: A total of 1226 patients with Stage II-IV FH tumors who received flank or abdominal RT in NWTS-3 and NWTS-4 were included in this analysis. Recurrent disease in the operative bed was classified as flank recurrence. Abdominal recurrence included all infradiaphragmatic tumor recurrences, including flank recurrences. This analysis included all flank/abdominal tumor recurrences, regardless of whether they might have been the initial or subsequent site of relapse. Based on the NWTS-1 results, RT delay was analyzed in two categories: 0-9 days and >or=10 days. RESULTS: The mean RT delay was 10.9 days; median delay was 9 days (range: 1-277 days). The RT delay was concentrated in a relatively narrow range of 8 to 12 days after nephrectomy in the majority of patients (59%). Univariate and multivariate analysis did not reveal RT delay of >or=10 days to significantly influence flank and abdominal tumor recurrence rates in NWTS-3 or NWTS-4. The 8-year flank tumor recurrence rates for 0-9 days and 10+ days RT delay were 1.9% and 1.2%, respectively (p value = 0.3). The 8-year abdominal tumor recurrence rates for 0-9 days and 10+ days RT delay were 4.8% and 5.3%, respectively (p value = 0.7). CONCLUSIONS: RT delay of >or=10 days did not significantly influence flank or abdominal tumor recurrence rates among children with FH tumors treated on NWTS-3 and NWTS-4. However, we were unable to test for a meaningful difference, because of the concentration of RT delay close to 10 days.

Abdominal Neoplasms↗
PubMed2006

Epstein-Barr virus-associated smooth muscle tumors are distinctive mesenchymal tumors reflecting multiple infection events: a clinicopathologic and molecular analysis of 29 tumors from 19 patients.

Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) are rare lesions that occur in immunocompromised patients. Because they have not been fully characterized pathologically or at the molecular level, we have studied 29 tumors from 19 patients, the largest series to date. Cases coded as EBV-SMT were identified in 19 patients from consultation files and from the renal transplant database at Singapore General Hospital. EBV-SMT occurred in adults (mean age 39 years; range, 21-57 years) and predominantly affected males (12 male, 7 female). Causes of immunocompromise were renal transplantation (10), AIDS (8), and steroid therapy (1). Tumors were located in soft tissue (5), lung (5), liver (4), and miscellaneous sites (15). In 13 patients (68%), the tumors were multiple. Infection with EBV was confirmed in all cases by in situ hybridization for EBV early RNAs (EBER). EBV-SMT were typically well-differentiated smooth muscle tumors with little atypia and usually a low level of mitotic activity. Unlike classic leiomyosarcomas, they lacked significant pleomorphism but frequently displayed primitive round cell areas and prominent intratumoral T lymphocytes. No consistent relationship between histologic features and clinical outcome was noted. All expressed actin (29 of 29) and less frequently desmin (14 of 26). Multiple tumors in a given patient were clonally distinct as assessed by the long terminal repeat region of the virus, supporting the view that multifocal tumors arise from multiple infection events rather than from metastasis. Strain typing by analysis of the EBNA-3C gene confirmed the presence of EBV type 2. Two of four tumors assessed were positive for a 30-bp deletion in the LMP1 gene. EBV copy number per cell ranged greatly between patients and between tumors from the same patient. Follow-up information was available in 18 of 19 patients (mean, 25 months; range, 1-105 months). Fifteen patients were alive: 11 with disease and 4 without. Three patients died, 1 due to disease. We conclude that EBV-SMT are histologically distinct from classic soft tissue smooth muscle tumors, are not readily evaluated by means of conventional histologic criteria, and in the case of multifocal tumors are the result of multiple infection events rather than metastasis. EBV-2 can transform smooth muscle cells, independent of the presence of the LMP1 deletion associated with greater virulence.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Wilms' tumor and other renal tumors of childhood: a selective review from the National Wilms' Tumor Study Pathology Center.

Selected studies of Wilms' tumor and related renal neoplasms in children, which have been based on the National Wilms' Tumor Study Pathology Center collection of more than 2,600 renal tumors of childhood, are reviewed. The purpose of the review is to illustrate the value of the collaborative approach to uncommon pathologic specimens and to distinguish several tumors often confused with Wilms' tumor, including renal adenocarcinoma, renal teratoma, and renal neurogenic tumors. The unfavorable prognostic significance of anaplastic cells in Wilms' tumor is emphasized. Two recently described clinicopathologic entities--clear cell sarcoma of kidney and malignant rhabdoid tumor of kidney--and morphologic variants often confused with Wilms' tumor or congenital mesoblastic nephroma of infancy are discussed. Clear cell sarcoma of kidney and malignant rhabdoid tumor of kidney are, apparently, distinctive neoplasms, not Wilms' tumor variants.

Adenocarcinoma↗
PubMed1997

Bone marrow-generated dendritic cells pulsed with tumor extracts or tumor RNA induce antitumor immunity against central nervous system tumors.

Recent studies have shown that the brain is not a barrier to successful active immunotherapy that uses gene-modified autologous tumor cell vaccines. In this study, we compared the efficacy of two types of vaccines for the treatment of tumors within the central nervous system (CNS): dendritic cell (DC)-based vaccines pulsed with either tumor extract or tumor RNA, and cytokine gene-modified tumor vaccines. Using the B16/F10 murine melanoma (B16) as a model for CNS tumor, we show that vaccination with bone marrow-generated DCs, pulsed with either B16 cell extract or B16 total RNA, can induce specific cytotoxic T lymphocytes against B16 tumor cells. Both types of DC vaccines were able to protect animals from tumors located in the CNS. DC-based vaccines also led to prolonged survival in mice with tumors placed before the initiation of vaccine therapy. The DC-based vaccines were at least as effective, if not more so, as vaccines containing B16 tumor cells in which the granulocytic macrophage colony-stimulating factor gene had been modified. These data support the use of DC-based vaccines for the treatment of patients with CNS tumors.

Animals↗