Caracterización de marcadores de células madre tumorales en cáncer escamocelular de cavidad oral

Introducción: El cáncer escamocelular de cavidad oral es una patología con bajas tasas de sobrevivencia. Cuando no es tratado adecuadamente es un tumor de alta recurrencia y resistente al tratamiento. Nuevas hipótesis plantean que las células tumorales progenitoras por sus propiedades de auto renovación, iniciación tumoral, migración y metástasis pueden ser responsables de la manutención y renovación de este tumor. Sin embargo, aún no existe un consenso sobre la verdadera participación de ellas, debido a que su identificación y caracterización es aún un reto experimental. Objetivo: En este trabajo se busca detectar células con expresión de marcadores de células tumorales Progenitoras en muestras cáncer escamocelular de cavidad oral y relacionarlo con los estadios de diferenciación del tumor. Metodología: En esta investigación se tomaron 32 muestras de pacientes con carcinoma escamocelular de cavidad oral. Se logró detectar in situ, mediante la técnica de inmunofluorescencia, cuatro reconocidos marcadores de células tumorales progenitoras. Resultados: Se identificaron los marcadores OCT4, SSEA4, NANOG y TRA-1-60 en los diferentes estadios de diferenciación tumoral, lo que sugiere la participación de las células progenitoras tumorales en la evolución de esta patología. Conclusiones: El establecimiento y correcta identificación de las células tumorales progenitoras abre nuevas vías terapéuticas para el abordaje de este tumor, en busca de mejorar el pronóstico, tasa de sobrevivencia y calidad de vida del paciente.

Introduction: Squamous cell carcinoma of the oral cavity is a pathology with poor survival rates. When it is not adequately treated, it is a tumor with high recurrence and resistance to treatment. According to new hypotheses, progenitor tumor cells, due to their properties of self-renewal, tumor initiation, migration, and metastasis, could be responsible for the maintenance and renewal of this tumor. However, there is still no consensus on their true participation, subsequent to difficult in their identification and characterization. Materials and methods: In this research, 32 samples provided from patients diagnosis with squamous cell carcinoma of the oral cavity were used. To detect specific markers progenitor tumor cells were used immunofluorescence microscopy. Results: The cells markers OCT4, SSEA4, NANOG and TRA-1-60 were identified in the different stages of the tumor samples, all these findings suggest the role of tumor progenitor cells in the evolution of this pathology. Conclusions: The establishment and correct identification of the progenitor tumor cells provide new therapeutic options for the approach of this tumor seeking to improve the prognosis, survival rate and quality of life of the patient.

Mixed germ cell tumour of testis: a case report with review of literature.

Testicular tumours are rare neoplasm. Mixed germ cell tumour is the most common histological variant. Essentially, any admixture of the germ cell tumours as seen in pure form may be seen, one of the most common admixtures being embryonal carcinoma and teratoma. Unfortunately many of these patients present late usually with some complications. We present a rare case of mixed germ cell tumour with predominant embryonal carcinoma and yolk sac tumour in adolescent patient with multiple metastatic foci at the time of presentation.

Antiproliferation and Redifferentiation in Thyroid Cancer Cell Lines by Polyphenol Phytochemicals

Thyroid carcinogenesis is accompanied by loss of thyroid-specific functions and refractory to radioiodine and thyroid stimulating hormone (TSH) suppression therapy. Redifferentiating agents have been shown to inhibit tumor growth and improve the response to conventional therapy. Polyphenol phytochemicals (PPs) in fruits and vegetables have been reported to inhibit cancer initiation, promotion, progression and induce redifferentiation in selected types. In this study we examined PPs induce redifferentiation in thyroid cancer cell lines. We investigated the effects of genistein, resveratrol, quercetin, kaempferol, and resorcinol on the F9 embryonal carcinoma cell differentiation model. The thyroid cancer cell lines, TPC-1, FTC-133, NPA, FRO, and ARO, displayed growth inhibition in response to genistein, resveratrol, quercetin. We further demonstrated that genistein decreased the dedifferention marker CD97 in NPA cells and resveratrol decreased CD97 in FTC-133, NPA, FRO cells and quercetin decreased CD97 in all cell lines. We observed increased expression of differentiation marker NIS in FTC-133 cells in response to genistein, and resveratrol but no change in NPA, FRO, ARO cells. Quercetin increased or induced NIS in FTC-133, NPA, FRO cells. These findings suggest that PPs may provide a useful therapeutic intervention in thyroid cancer redifferentiation therapy.

Enhanced Cardiomyogenic Differentiation of P19 Embryonal Carcinoma Stem Cells

BACKGROUND AND OBJECTIVES: We investigated the effects of different concentrations of serum, 5-azacytidine, and culture time on the cardiomyogenic differentiation of P19 embryonal carcinoma stem cells in the course of developing an efficient protocol for generating the cardiomyogenic lineage. MATERIALS AND METHODS: P19 cells were plated at a density of 1x10(6) cells on 10-cm bacterial dishes for 96 hours in the presence of 1% dimethyl sulfoxide to form embryoid bodies. The embryoid bodies were cultured in medium with 2% or 10% fetal bovine serum for an additional 10 or 15 consecutive days in the presence of 0, 1, or 3 microM 5-azacytidine. RESULTS: Quantitative real-time polymerase chain reaction (PCR) analysis showed that the messenger ribonucleic acid (mRNA) expression of cardiac muscle-specific genes, such as GATA4, alpha-actin, alpha-myosin heavy chain, and cardiac troponin T, were significantly higher in the 15-day culture groups than in the 10-day culture groups. Furthermore, the cardiac muscle-specific genes were expressed more in the high-serum groups compared to the low-serum groups regardless of the culture time. Cardiomyogenic differentiation of the P19 cells was most effective in 1 microM 5-azacytidine regardless of the serum concentrations. In addition, the stimulation effects of 5-azacytidine on cardiomyogenic differentiation were more significant under low-serum culture conditions compared to high-serum culture conditions. Cardiomyogenic differentiation of P19 cells was further confirmed by immunostaining with cardiac muscle-specific antibodies. CONCLUSION:Taken together, these results demonstrated that cardiomyogenic differentiation of P19 cells was enhanced by a combination of different experimental factors.

Diffuse Embryoma of the Testis: A Case Report

Diffuse embryoma of the testis is a very rare, distinct form of mixed germ cell tumor. I report here on a case of diffuse embryoma in a 22-year-old male who presented with painful scrotal swelling. The resected testis was entirely occupied by a non-encapsulated tumor mass. The cut surface of the tumor was grey or whitish pink, soft and granular with foci of hemorrhage and necrosis. Microscopically, the tumor was characterized by a diffuse, orderly arrangement of embryonal carcinoma and yolk sac tumor in almost equal proportions. The yolk sac tumor component was diffusely wrapped around the embryonal carcinoma. Syncytiotrophoblasts were scattered throughout the tumor. Minor foci of immature teratoma, seminoma and intratubular germ cell neoplasia were observed. The yolk sac tumor (YST) component was emphasized by immunoreactivity for alpha fetoprotein, whereas the embryonal carcinoma was reactive for CD30. The strong reactivity for cytokeratin in the YST component formed an outstanding contrast to the weak cytokeratin reactivity in the embryonal carcinoma.

Teratomas in Children

Among 60 children with teratoma, forty-three (71.7 percent) were girls and 17 (28.3 percent) boys. Primary sites were sacrococcygeal in 30 patients (50 percent), retroperitoneal in 12 (20 percent), ovarian in 11 (18.3 percent), testicular in 3 (5 percent), and one in each of nasopharyngeal, gastric, hepatic and pancreatic (1.6 percent, respectively). Fifty-five (91.7 percent) teratomas were benign and 5 (8.3 percent) malignant. Malignant teratomas were detected only at sacrococcygeal region (16.7 percent). Older than 2 months of age at diagnosis, presence of urinary and colonic obstructive symptoms, multiple masses and elevated serum alpha-fetoprotein were indicators of malignancy in sacrococcygeal region. Tumor size, presence of calcification, and gross appearance (cystic or solid) did not correlate with malignant nature. Thirteen (21.7 percent) cases were associated with other anomalies. For the immature teratoma, the operative resection without adjuvant chemotherapy was enough. Three malignant cases were survived, one with chemotheapy for 3 years and the others without chemotherapy for 5 and 10 years.

A Case of Primary Mediastinal Embryonal Carcinoma Arising in the Posterior Mediastinum / 결핵

Primary germ cell tumors of the mediastinum are rare, accounting 1-5% among all germ cell tumors and 10% of all neoplasms in this area. Approximately 85% of these tumors occur in men with a mean age 29 years. These tumors are mainly found in the anterior mediastinum and appear grossly as large lobulated masses. They are frequently invasive at the time of diagnosis and almost 90% of patients are symptomatic. Primary nonseminomatous germ cell tumor arising in the posterior mediastinum is very rare. We report a case of 37- year old male arising from the posterior mediastinum. Serum tumors markers including alpha-fetoprotein and beta-hCG which are usually elevated in germ cell tumor were not elevated. He was found to have a primary mediastinal embryonal carcinoma with pulmonary metastasis at open exploration. He was treated with debulking surgery and cisplatin-based chemotherapy, died of sepsis after 15 months postoperatively.

A Case of Mixed Germ Cell Tumor in the Third and Lateral Ventricle

The authors report a case of mixed germ cell tumor arising at the third ventricle and extending to the lateral ventricle in a sixteen-year-old male who presented with headache, nausea, vomiting and polydipsia. Magnetic resonance imaging of the brain demonstrated a lobulated mass in the third and left lateral ventricle. For surgery, the anterior interhemispheric transcallosal approach was used, and on histologic examination three concurrent histologic components were found: germinoma, embryonal carcinoma, and endodermal sinus tumor.

Three cases of primary mediastinal Nonseminomatous germ cell tumors / 결핵

Primary mediastinal nonseminomatous germ cell tumor is extremely rare. Apart from rarity and large size, mediastinal germ cell tumors show striking similarity to testicular tumors in age, incidence, and tumor type. The symptoms associated with these tumors are related mainly to size, invasion of neighboring structures, and distant metastases. Tissue diagnosis is obtained by biopsy of the primary lesion or by biopsy of metastatic sites. Tumors often present with advanced bulky disease, which are unresectable. So these tumors require an aggressive multidisciplinary approach to management. Optimal management includes aggressive surgical debulking and early use of cisplatin-bleomycin-based combination chemotherapy. Serial biomarker measurements permit early recognition of recurrence and improved timing of surgical intervention. The prognosis for mediastinal germ cell tumors is poor, not only because they are far advanced at the time of diagnosis but also because some of the tumors-such as embryonal carcinomas, choriocarcinomas, and endodermal sinus tumors-are very aggressive. In these cases, we present three young male patients with large mass on anterior mediastinum. Tissue diagnosis was obtained by primary lesion biopsy. All patients received surgical debulking and combination chemotherapy and experienced a brief response and eventually had relapses. We report these cases with a review of literatures.

A Clinical Observation of 13 Testicular Embryonal Carcinomas / 대한비뇨기과학회지

We reviewed 13 patients with testicular embryonal carcinoma from July 1982 to May 1994. Embryonal carcinoma accounted for about 25% of total testicular tumors(13/56) and about 34% of nonseminomatous germ cell tumors(13/38). Among the patients with embryonal carcinoma, about 85% were diagnosed in the 15-to-34 year age group. About seventy percent of the patients had metastatic disease at the time of diagnosis and 66.7% of these had distant metastasis including by lung, bone, retroperitoneal lymph node and cervical lymph node, attesting to the aggressiveness of embryonal carcinoma and its tendency to early hematogenous spread. Serum AFP was elevated in 10 patients(76.9%) and hCG in 6 patients(46.2%). All patients with stage I (4/13) were treated with radical orchiectomy only, and all patients with stage II(3/13) were treated with radical orchiectomy and retroperitoneal lymph node dissection(RPLND) followed by chemotherapy. Of the patients with stage III(6/13), 4 patients were treated with radical orchiectomy and chemotherapy, and 2 patients with radical orchiectomy and early chemotherapy, followed by RPLND. The pathologic findings of lymph node at the time of RPLND in stage III were 1 residual embryonal carcinoma and 1 fibrosis. In stage I and II, all patients were still alive. In stage III, 2 patients were still alive for 22 and 48 months. Among the 4 expired patients, 2 were from lung metastasis and the others from sepsis might caused by chemotherapy. These results suggest that the radical orchiectomy only with close clinical observation for stage l had a good survival, and long term survival in stage II patients treated with radical orchiectomy and RPLND followed by chemotherapy will be expected. And in stage III, if the side effects of the chemotherapy is reduced, the better survival may be obtained.

Two Cases of Embryonal Carcinoma / 日本農村医学会雑誌

We show two cases of embryonal carcinoma and discuss the results treatment in this paper. Although the progress of this malignant tumor after treatment was not related to the stadium of the progress of disease, it was found related to the amount of serum AFP and to the immaturity of this neoplasm. In view of the latent metastasis, the combination chemotherapy with Cisplatin was deemed necessary. The dose intensity must be kept 1. Also, we considered it necessary to prescribe the medicine to the patients more than 6 cycles.

Metastatic Embryonal Carcinoma of Testis: Aspiration Cytology of Cervical Lymph Node

Embryonal carcinoma of testis may be composed of primitive cells with epithelial appearance showing prominent variation in size and shape, clear cytoplasm, overlapping nuclei. and many mitoses. Multiple lymph node enlargement was noticed in a 45-year-old man with known huge testicular tumor, 20 x 15 cm, and clinically malignant lymphoma was suspected. Microscopic and cytologic finding of both biopsy and needle aspiration from neck lymph node disclosed highly undifferentiated large cells, mostly in solid sheets and often forming glandular spaces. Massive necrosis was observed. Cytologic diagnosis of embryonal carcinoma was made possible, relied on the result of immunohistochemistry that revealed negative LCA, and positive cytokeratin and CEA as well as the cytologic features. Serum levels of HCG and AFP of the patient, in addition, were markedly elevated.

Endodermal Sinus Tumor of the Orbit

An endodermal sinus tumor is a malignant germ cell tumor that usually arises in the gonads, but on rare occasion occurs in extragonadal locations. Our case was that of a 3 year old girl who complained of a rapid growing orbital mass. On histologic examination it revealed the typical picture of an endodermal sinus tumor and it also disclosed a positive reaction for alphafetoprotein using an immunoperoxidase technique. An orbital exenteration was performed followed by chemotheraphy, but the patient died 5 months after the onset of the disease.

Large Mononuclear Cells in Seminoma: An Immunohistochemical Analysis of 21 Cases

Twenty-one cases of seminoma (including testicular seminoma, ovarian dysgerminoma and extragonadal germinoma) were reviewed for the cell types responsible for the production of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG). Histologically the cases included seventeen classical seminomas and 4 anaplastic seminomas. The latter had some mononuclear and multinuclear giant cells. All 4 patients with anaplastic seminoma had elevated levels of serum AFP, and each of these cases contained AFP producing tumor cells identified by immunoperoxidase staining. All seminomas of patients with elevated serum levels of HCG were of the classical type but HCG producing tumor cells could not be identified by immunoperoxidase staining. Immunoreactivity to anti-AFP was found in some large mononuclear cells and anaplastic cells. To explain these results, we propose that the large mononuclear cell is a multipotential cell capable of differentiating into a germ cell, yolk sac and embryo, and that the anaplastic seminoma cells might represent a stage on the continuum of cellular differentiation from the large mononuclear cells to germ cells. The multinuclear giant cell does not appear to be essential for the production of either AFP or HCG in seminoma.

Induced differentiation and gap junction formation of murine embryonal carcinoma cells / 中国病理生理杂志

Based on the work we have previously done, the experiments presented here indicate that ?aS1, a mutant of the P19 line of routine embryonal carcinoma (EC) cells, can be induced to differentiate by retinoic acid (RA), but is not sensitive to DMSO. Also there is a dynamic equilibrium achieved by a balance between the processes of ?aS1 cell proliferation and differentiation when exposed to certain RA concentrations. The ?aS1 cell has a lower ability for forming gap junctions as compared with the other mutants, showing that EC cell mutants could be defective in the development of a certain gap junction type. In the RA-treated mixed aggregates of P19 and RAJH6, only P19 cells differentiated continuously but the surviving fraction of RAJH6 cells in the presence of 6-TG kept unchanging. The result suggests that the undifferentiated and differentiating EC cells can be metabolically coupled by gap junctions. Our work may further the understanding of cell differentiation, congenital abnormality and tumor reversion.

A Case of Mixed Germ Cell Tumor at Right Frontal Area (Embryonal Carcinoma With Germinoma)

Primary intracranial germ cell tumor is rare. The majority of these tumors are germinoma and teratoma of varying degree of differentiation with much less frequent occurrence of embryonal carcinoma, choriocarcinoma and endodermal sinus tumors. These may occur in various mixture. These are almost exclusively situated in the midline with the pineal or parapineal and hypothalamus. We are presenting a case of embryonal carcinoma mixed with germinoma component, which occurred to a 20 year old man who underwent operation and radiation therapy 6 months previously and the tumor mass was located at the right frontal area extending to the base of frontal lobe. We removed the mass near totally and radiation therapy was performed. The result was successful so far.

A Case of Embryonal Carcinoma Developed in a Cryptorchid Testis / 대한비뇨기과학회지

A case of testicular embryonal carcinoma developed in s cryptorchid testis is presented with a review of the literature. According to Campbell's series, the incidence of malignant cryptorchid testis was 11.6%. and his statistical evaluation was similar to Gilbert and Hamilton's series of 7,000 cases of testicular neoplasms where 840 tumors were developed in undescended testes(12%). Both authors agree that the chance of neoplastic development in a cryptorchid testis is approximately 48 times greater then that developing in a normally descended testis. Several cases of testicular tumor were reported sporadically in Korea, but malignant tumors in cryptorchism were rarely seen in the literatures Only two cases of malignant cryptorchid testis were already reported in Korea.