Malignant Cell Tumors Research Articles

A Demographic Study on Oral Non Squamous Cell Malignant Tumors

Background: Nonsquamous cell malignant tumors of jaw and oral soft tissue are rare constituting between 6%-10% of all malignancies in the region. A few case reports of individual tumors are available while reviews of significant series is lacking. This report presents 22 cases of Nonsquamous cell malignant tumors collected over 8 months at a tertiary oral care centre in Dhaka, Bangladesh. Objective: To find out the distribution & pattern of oral nonsquamous cell malignant tumors among all oral malignancy and to find out the age, sex, site, clinical presentation, the histological types of these tumors. Method: This descriptive cross sectional study was done in Oral and Maxillofacial Surgery Department, Dhaka Dental College and Hospital.The entire patient histopathologically diagnosed as any type of Nonsquamous cell tumor were selected. Data were collected in a summarized data sheet. Then histopathological types of them were analyzed to indicate the distribution according to age, gender, site and clinical presentation. Result: There were 107 Oral malignancies of which 22(20.56%) were Nonsquamous cell malignant tumors which is significant in comparison to Squamous cell carcinoma in Bangladesh. Among the respondents, 9(40.91%) were diagnosed as minor salivary glands malignant tumors, 7(31.2%) were diagnosed as sarcomas, Malignant melanoma were 4(18.18%) and Non- Hodgkin’s lymphoma were 2(9.09%). The male to female ratio was 1:1.2 with ages were between 9 years to 70 years old (mean age 35.45 ± 21.76 years) with most patients (36.36%) in 16 to 30 years of life. Cases presented with symptoms such as swelling (100%), pain, paresthesia, loose tooth and tissue ulceration. Conclusion: In Dhaka Dental College Hospital, nonsquamous cell malignant tumors account for 20.56% of all oral malignancies among them minor salivary glands malignant neoplasm and malignant melanoma were the predominant type. Most affected were people in the 2nd and 3rd decades of life with no sex predilection. Most common site of involvement was maxilla. The need for improved medical awareness, diagnostic facilities and upgrading of infrastructure was stressed. DOI: http://dx.doi.org/10.3329/updcj.v3i2.17997 Update Dent. Coll. j: 2013; 3 (2): 34-38

A De Novo Unclassified Malignant Spindle Cell Neoplasm of Liver Allograft

Spindle cell neoplasms are rarely reported in liver allografts; most are benign and associated with Epstein-Barr virus infection. We present a case of a malignant spindle cell neoplasm arising in a liver allograft. The patient underwent orthotopic liver transplant for cirrhosis secondary to nonalcoholic steatohepatitis. After 2 years, he presented with vague abdominal complaints. Imaging studies revealed a 10-cm right hepatic lobe mass. The patient underwent right-sided hepatectomy. The tumor displayed areas of broad, relatively hypocellular fascicles, whorls, and perivascular clustering; spindle cells with mild to moderate nuclear pleomorphism; and relatively abundant eosinophilic cytoplasm. Mitotic activity ranged from 2 to 4 mitotic figures per 20 high-power fields. Immunostaining displayed positivity for epithelial membrane antigen, vimentin, CD99, BCL2, cytokeratin, and human herpesvirus 8. Interphase fluorescence in situ hybridization findings were negative for a translocation involving the SS18 gene (18q11). We believe the tumor represents the first reported case of a novel unclassified spindle cell malignant neoplasm in a liver allograft.

Експресія генів IGFBP1, IGFBP2 та IGF2BP3 у клітинах гліоми з пригніченою функцією сигнального ензиму ERN1 за умов дефіциту глутаміну і глюкози

Insulin-like growth factor binding proteins play an important role in the regulation of cell proliferation and malignant tumor growth. It was shown that blockade of both enzymatic functions of sensor and signaling enzyme ERN1 (from endoplasmic reticulum to nuclei-1), the major component of endoplasmic reticulum stress signaling, decreases the expression level of IGFBP1, IGFBP2 and IGF2BP3 genes in U87 glioma cell. The decreased level of these gene expressions in glioma cells with ERN1 signaling enzyme loss of function correlates with suppression of cell proliferation. It was shown that glutamine deprivation condition leads to enhance the expression of IGFBP1 gene, but did not change significantly the expression of IGFBP2 and IGF2BP3 genes in both types of glioma cells. Moreover, this effect of glutamine deprivation did not depend from suppression of ERN1 enzyme function. At the same time, the expression of IGFBP2 and IGF2BP3 genes is decreased in glucose deprivation condition in both types of glioma cells and blockade of ERN1 signaling enzyme enhanced this effect. Thus, results of this investigation demonstrated that the expression of IGFBP1, IGFBP2 and IGF2BP3 genes in U87 glioma cells is dependent from signaling enzyme ERN1 and is changed in glutamine and glucose deprivation conditions, but only effect of glucose deprivation was depended of ERN1 signaling enzyme function. Moreover, the decreasing of IGFBP1, IGFBP2 and IGF2BP3 gene expressions in glioma cells with blockade of both enzymatic activities of ERN1 is possibly related to suppression of these cells proliferation.

Diagnostic value of CT perfusion imaging for parotid neoplasms

To assess the value of CT perfusion imaging in the differentiation of different histological categorization of benign tumours from malignant tumours in patients with parotid neoplasms. CT perfusion was successfully performed in 62 patients with parotid neoplasms whose diagnoses were confirmed by surgery or biopsy. The software generated a tissue time-density curve (TDC) and measured blood volume, blood flow, mean transit time and capillary permeability surface product. One-way ANOVA and receiver operating characteristic curves were used to analyse the difference and diagnostic efficacies of all perfusion data between each one of the benign tumours and malignancies. Statistical significance was assigned at the 5% level. Pleomorphic adenomas mainly had a gradually ascending TDC. Warthin tumours showed a fast ascent followed by a fast descent. The TDC of basal cell adenomas had a fast ascension followed by a plateau, then a gradual descent. Malignant tumours mainly showed a rapidly ascending curve with a stable plateau. Significant differences were observed in blood flow, blood volume and mean transit time between pleomorphic adenomas and malignant tumours (p < 0.05) as well as in blood flow and blood volume between the Warthin tumours, the basal cell adenomas and the malignant tumours (p < 0.05). Differences in permeability surface between the basal cell adenomas and malignant tumours were significant (p < 0.01). CT perfusion of parotid gland could provide TDC and perfusion data, which were useful in the differentiation of different histological benign tumours and malignant tumours in the parotid gland.

A Study of Gata3 and Phox2b Expression in Tumors of the Autonomic Nervous System

Autonomic neurons and chromaffin cells, which constitute the autonomic nervous system, are derived from a common progenitor from the neural crest, and its development is controlled by a network of transcription factors, including the master regulator, Phox2b, and its downstream, Gata3. Anti-Phox2b and anti-Gata3 antibodies were applied to a total of 77 autonomic nervous system tumors, including 35 paragangliomas, 21 pheochromocytomas, 9 neuroblastomas, 4 ganglioneuroblastomas, and 8 ganglioneuromas, as well as their potential morphologic mimics, including tumors of the small round cell tumor group, neuroendocrine carcinomas of lung and gastrointestinal tract (carcinoid tumors/neuroendocrine tumors, large cell neuroendocrine carcinomas, and small cell carcinomas), Merkel cell carcinomas, benign and malignant tumors of thyroid, parathyroid, and adrenal cortex, and malignant melanomas. A variety of nonendocrine/neuroendocrine carcinomas were also studied. Gata3 expression was seen in 89% of paragangliomas, 95% of pheochromocytomas, and all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas, as well as in all parathyroid tumors, a majority of urothelial and mammary carcinomas, and a subset of squamous cell carcinomas, but all other tumors were negative. Phox2b expression was seen in all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas and in 40% of paragangliomas, but pheochromocytomas and all other tumors were negative. Gata3 is a highly reliable marker for paragangliomas, pheochromocytomas, and neuroblastic tumors to distinguish from their simulators. This is an additional utility for this marker, which is used for the diagnosis of urothelial and mammary carcinomas. Phox2b is also highly specific, but its low sensitivity to paragangliomas and pheochromocytomas would limit the utility only to neuroblastic tumors.

Oxidative stress and MAPK involved into ATF2 expression in immortalized human urothelial cells treated by arsenic

ATF2 is a subfamily member of AP-1 and has an important role in cellular stress responses. ATF2 has been implicated in a transcriptional response leading to cell migration and malignant tumor progression. However, little is known about the effect of arsenic on expression of ATF2 and regulatory pathways in human urothelial cells. In this study, ATF2 expression was measured in NaAsO(2)-treated human uroepithelial cell line (SV-HUC-1) with 1, 2, 4, 8 and 10 μM concentrations in order to provide some basis data for the study on mechanism of bladder cancer induced by arsenic. We found that ATF2 expression levels at 2, 4, 8 and 10 μM arsenic-treated cells were significantly higher than those of control cells, and the strongest expression occurred in 4 μM NaAsO(2)-treated cells. Antioxidants (melatonin) and JNK or p38 inhibitors decreased significantly arsenic-induced ATF2 expression. Taken together, these data indicated that the increasing of ATF2 expression is mediated via oxidative stress induced by arsenic in SV-HUC-1 cells, and JNK or p38 rather than ERK is responsible for arsenic-induced ATF2 expression. ROS were also involved in arsenic induced the activation of JNK and p38 MAPK signaling pathway.

Abstract 3592: Roles of miR-199a-5p and COX-2 in arsenic-induced tumor angiogenesis.

Abstract Arsenic is a well-known human carcinogen which is closely associated with lung cancer. However, the mechanism underlying the arsenic-induced carcinogenesis remains to be elucidated. The alterations of miRNAs profiles in cancers have profound implication in cancer development. However, it remains to be determined whether the alterations of miRNA signature in response to carcinogens such as arsenic may result in cell malignant transformation and tumor growth. In this study, we developed an in vitro model by transforming human lung epithelial BEAS-2B cells through long-term exposure to low concentration of arsenic. The BEAS-2B cells were malignantly transformed validated by cell proliferation, anchorage independent growth and tumor growth assay. By utilizing this model, we found that miR-199a-5p expression level was dramatically repressed in arsenic-transformed cells. Re-expression of miR-199a-5p impaired arsenic-induced tumor angiogenesis through directly targeting hypoxia inducible factor-1α (HIF-1α). Interestingly, we found another proangiogenic factor cyclooxygenase-2 (COX-2) that was also upregulated in arsenic-transformed cells and was predicted as a target of miR-199a-5p. It was confirmed by generating COX-2 3’UTR miRNA luciferase reporters with wild-type or mutant binding sites with miR-199a-5p. Overexpression of miR-199a-5p inhibited COX-2 protein expression. Functional study revealed that knockdown of COX-2 by siRNA in arsenic-transformed cells decreased tumor angiogenesis. We further showed that the COX-2 promoter contains a functional hypoxia response element (HRE). HIF-1α regulated COX-2 expression at the transcriptional level via direct binding to the HRE (-576/-584) located within the COX-2 promoter. Thus, arsenic-induced COX-2 activation is mediated by repression of miR-199a-5p and activation of HIF-1. Moreover, prostaglandin E2 (PGE2), a product of COX-2 regulated HIF-1 expression in a positive-feedback manner. In addition, arsenic-transformed cells have high levels of reactive oxygen species (ROS) for activating COX-2 pathway. Taken together, our results demonstrate that arsenic-induced angiogenesis through miR-199a-5p repression and pro-inflammatory responses induced by ROS. Both pathways lead to activation of HIF-1/COX-2 pathway. These findings establish critical roles of miR-199a-5p and its downstream targets HIF-1/COX-2 in arsenic-induced tumor angiogenesis. As miR-199a-5p is generally downregulated, whereas COX-2 is overexpressed in human lung cancer tissues, they may be used as new therapeutic targets for lung cancer treatment in the future. Citation Format: Jun He, Richard Carpenter, Yue Jiang, Qing Xu, Bing-Hua Jiang. Roles of miR-199a-5p and COX-2 in arsenic-induced tumor angiogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3592. doi:10.1158/1538-7445.AM2013-3592

Multicenter randomized controlled clinical study for the operative treatment of malignant ovarian germ cell tumors

To investigate the operative treatment for first-treated patients with malignant ovarian germ cell tumors who need preservation of fertility. The clinical data of 105 patients who were treated with fertility-sparing surgery in 11 hospitals from 1992 to 2010 were collected to evaluate the outcomes of different primary surgical operative procedures. All 105 cases were performed the surgeries that preserved fertility and divided into three groups according to the surgical approaches, comprehensive staging surgery group: 47 cases (44.8%) received comprehensive staging surgeries that including the ipsilateral oophorectomy + omentectomy + retropertoneal lymph node dissection ± appendectomy + multiple biopsies;oophorectomy group:45 cases (42.9%)received ipsilateral oophorectomy ± biopsy of contralateral ovary ± omentectomy;tumor resection group:13 cases (12.4%) received enucleation of the mass with preservation of the ovary. Differences were compared among the three groups of patients in the surgery-related indicators, complications, fertility and prognosis. (1) Surgery-related indicators:the average blood loss of the comprehensive staging surgery group, the oophorectomy group and the tumor resection group were 496, 104 and 253 ml, the mean operation time were 176, 114 and 122 minutes, respectively, and there were significant differences among three groups (P = 0.011, P = 0.000). (2) Complication:the surgical complication rates of the three groups were 17% (8/47), 0 and 1/13, with significant differences (P = 0.015). (3) Reproductive function status: the pregnancy rate and birth rate of the three groups were no significant differences (9/19 vs. 7/19 vs. 2/3, P = 0.515; 8/19 vs. 5/19 vs. 2/3, P = 0.636). (4) PROGNOSIS: the recurrence rate of the three groups were significant differences [13% (6/47) vs. 0 vs. 2/13, P = 0.013], but the death rate with no significant differences [6% (3/47) vs. 0 vs. 0, P = 0.129]; The five-year survival rate of three different groups were 89%, 100% and 100% (P > 0.05), while disease free survival rate were 85%, 100% and 83% (P < 0.05), respectively. Compared with comprehensive staging surgery, oophorectomy group have higher surgical security and satisfactory prognosis, considerable pregnancy rates and birth rate. The tumor resection security may be reliable, but the prognosis is poor.

Small cell malignant tumors of bone: comparison between diagnosis using core needle biopsies and surgical specimens

To compare the pathologic diagnosis and immunohistochemistry of small cell malignant tumors (SCMT) of bone using both core needle biopsy and surgical specimen. Seventy-seven cases of SCMT with core needle biopsies and surgical specimens available were respectively analyzed by histologic examination and immunohistochemical study, with literature review. The male-to-female ratio was 48:29. The age of the patients ranged from 6 to 73 years. The tumors studied included Ewing sarcoma/PNET (n = 38), myeloma (n = 23), lymphoma (n = 10), small cell osteosarcoma (n = 2), small cell carcinoma (n = 2) and mesenchymal chondrosarcoma (n = 2). The tumors involved limbs, axial skeleton and flat bones. Microscopically, the tumors shared similar histology, with small round cells and spindly cells arranged in diffuse sheets. The pathologic diagnosis by core needle biopsies correlated with that by surgical specimens in 84.4% (65/77) of the cases. SCMT represents a heterogeneous group of malignancy. Correlations with clinicoradiologic findings and application of ancillary investigations including immunohistochemistry and molecular study are important for definitive diagnosis. Pathologic diagnosis using core needle biopsies shows good results and provides useful information for surgical planning.

Clear cell atypical fibroxanthoma: a case report and brief review of the literature

Aim/Background Clear cell tumours of the skin present a diagnostic challenge. We report a case of clear cell atypical fibroxan-thoma (clear cell AFX) and discuss differential diagnosis of clear cell tumours of skin. We also briefly review literature and immuno-histochemical testing pertaining to this group of lesions. Case presentation A 75-year-old male presented with an ulcerated lesion on the forehead/scalp. There was a past history of Gleason 3 + 4 = 7 prostatic acinar adenocarcinoma. The case was reported in consultation with a second expert dermatopathology opinion. Discussion The differential diagnosis of clear cell tumours of skin is broad and includes epidermal proliferations, clear cell adnexal lesions, melanocytic proliferations, mesenchymal lesions and metastases. In this case the lesion was pleomorphic and dermally based. This limited possible diagnoses to balloon cell melanoma, clear cell AFX, clear cell squamous cell carcinoma (SCC), clear cell basal cell carcinoma (BCC) and malignant skin adnexal neoplasms (sebaceous carcinoma, tricholemmal carcinoma and clear cell malignant eccrine neoplasms). Metastases, mesenchymal neoplasms (dermatofibroma with ‘monster’ cells and leiomyosarcoma with clear cell change) and non-neural granular cell tumour of the skin were also considered. Conclusion AFX is a diagnosis of exclusion. This case demonstrates how a comprehensive immunopanel and morphological features are used to eliminate other possibilities.

Cytokeratin-positive interstitial reticulum cell sarcoma: Extranodal presentations mimicking carcinoma

Cytokeratin-positive interstitial reticulum cell (CIRC) sarcoma is a rare type of dendritic cell tumor derived from a subset of fibroblastic reticular cells. Expression of cytokeratins and extranodal location of these tumors can lead to a misdiagnosis of carcinoma. We report two cases of CIRC sarcomas primarily involving the scalp and breast. Patients were referred with an initial diagnosis of carcinoma. Case 1 underwent wide local excision of the scalp tumor with left posterolateral neck dissection. Case 2 had modified radical mastectomy for the tumor in left breast. Histopathological examination of both specimens showed an epithelioid to spindle cell malignant tumor that co-expressed CK 8, CK 18, vimentin, and smooth muscle actin. A diagnosis of CIRC sarcoma was made. Pathologists should be aware of this subset of dendritic cell sarcoma. Carcinomas, other sarcomas of the accessory dendritic cell family, and poorly differentiated malignant tumors have to be ruled out by combination of morphology, immunohistochemistry, and electron microscopic studies.

The role of preoperative transarterial embolization in spinal tumors. A large single-center experience

Background contextPatients with spinal tumors are often referred for preoperative angiography and embolization before surgical resection to minimize intraoperative bleeding. PurposeThe purpose of the present study was to investigate the angiographic appearance of a variety of spinal tumors, assess the safety and efficacy of preoperative embolization in relation to the amount of intraoperative blood loss, and correlate intraoperative tumor histology with the degree of gadolinium enhancement on spinal magnetic resonance imaging (MRI) and tumor vascularity visualized during angiography. Study design/settingRetrospective and single-institution cohort study. Patient sampleOne hundred four patients with spinal tumors referred for preoperative embolization. Outcome measuresEffectiveness of preoperative embolization in relation to intraoperative blood loss and number of transfused packed red blood cell units in perioperative period (72 hours). MethodsFrom 2000 to 2009, 104 patients with spinal tumors underwent 114 spinal angiographies with the intent to embolize feeder vessels before surgery. The effectiveness of embolization was compared with the documented intraoperative blood loss. Angiographic tumor vascularity was graded from 0 (avascular) to 3 (highly vascular). Ninety-four patients had a pre– and post–gadolinium-enhanced MRI of the spine before transarterial embolization. Magnetic resonance imaging vascular enhancement was classified as Grade 3 (avid contrast enhancement), Grade 2 (moderate), or Grade 1 (mild). ResultsTransarterial tumor embolization was angiographically complete in 63 (66%) and partial in 33 procedures (34%). In 18 cases, the target was not deemed suitable for embolization. A limited statistical analysis did not reveal a statistical difference in documented intraoperative blood loss between patients with complete versus partial embolization for the entire cohort or when stratified into renal cell carcinoma (RCC; p=.64), multiple myeloma (p=.28), malignant (p=.17) and benign tumor groups (p=.26). There were no clinical complications associated with embolization. There was poor correlation between MRI enhancement and angiographic vascularity. ConclusionsPreoperative embolization was angiographically effective in most cases. Avid gadolinium enhancement (Grade 3) on MRI was not predictive of hypervascularity on angiography. Furthermore, hypervascularity was not restricted to classically vascular tumors, such as RCC, as it was noted in some patients with breast and prostate cancer. However, with the available numbers, the quality of preoperative embolization did not significantly affect intraoperative blood loss. A future prospective randomized controlled study may be warranted to better characterize the benefits of preoperative embolization for spinal tumors.

Utility of NUT gene expression and rearrangement in diagnosis of NUT midline carcinoma in upper respiratory tract

To investigate the importance of expression of the NUT gene and its rearrangement in diagnosing NUT midline carcinoma (NMC) of the upper respiratory tract; and to evaluate the prevalence, histological features and differential diagnosis of NMC of the upper respiratory tract. One-hundred and sixty-three small cell malignant tumors of the upper respiratory tract were reviewed at the Beijing Tongren Hospital, Capital Medical University over a 20-year period. These cases included poorly-differentiated squamous cell carcinomas (n = 31), undifferentiated carcinoma (n = 1), non-keratizing undifferentiated nasopharyneal carcinomas (n = 60), small cell neuroendocrine carcinomas (n = 6) and non-epithelial small round cell malignant tumors (n = 65). The clinical and pathologic features were investigated. All cases were subjected to Epstein-Barr virus encoded RNA (EBER) in situ hybridization and NUT monoclonal antibody immunohistochemical staining. Cases positive for NUT immunohistochemistry and negative for EBER in situ hybridization were submitted for fluorescent in situ hybridization (FISH) for rearrangements in both BRD4 and NUT genes, and immunohistochemical staining for a set of cytokeratins (AE1/AE3, CK7, CK8), p63,and neuroendocrine markers (NSE, Syn, CgA, S-100 protein, CD56). Three cases of poorly-differentiated squamous cell carcinomas and one case of undifferentiated carcinoma showed diffuse nuclear immunohistochemical staining with antibody against NUT. These positive cases approximately accounted for 12.5% (4/32) of this group, 4.1% (4/98) of the malignant epithelial carcinomas and 2.5% (4/163) of all small round cell malignant tumors in the study. The age of these patients were 42 - 59 years. Other groups were all negative for NUT immunohistochemistry. These four cases also stained for antibodies against cytokeratins and p63, but were negative for neuroendocrine markers and not associated with EBV infection. Only two of these four cases showed rearrangements of the NUT and BRD4 genes by FISH. These two patients died within one year. The other two patients that did not demonstrate NUT rearrangement by FISH were alive and did not have an aggressive clinical course, surviving 40 and 12 months respectively. NMC is a rare small round cell malignant tumor in the upper respiratory tract. Only in the groups of primary poorly differentiated squamous cell carcinoma and undifferentiated carcinoma were positive for NUT immunohistochemical staining and NUT rearrangement by FISH. NMC typically occurs in midline organs, and affects the sinonasal tract. It is not associated with EBV infection. There is difference in the clinical course and prognosis among NMC patients. NUT immunohistochemical staining and NUT gene rearrangement analysis can differentiate NMC from other small cell tumors in the upper respiratory tract.

Pathologic Characteristics of NUT Midline Carcinoma Arising in the Mediastinum

NUT midline carcinomas (NMCs) comprise a group of highly aggressive tumors that have been reported primarily in the head, neck, and mediastinum of younger individuals. These tumors overexpress the nuclear protein in the testis (NUT), most commonly due to a chromosomal translocation that fuses the NUT gene on chromosome 15 with the BRD4 gene on chromosome 19. Although the earliest recognized cases were described in the thymus or mediastinum, an extensive survey for NMCs among malignant thymic or other mediastinal neoplasms has not been reported. We examined NUT expression in 114 cases of poorly differentiated carcinomas or unclassified mediastinal malignancies using a clinically validated NUT-specific monoclonal antibody. Four of 114 (3.5%) cases showed nuclear NUT expression. A NUT translocation was confirmed by fluorescence in situ hybridization in 3 of these cases. These tumors arose in 2 men and 2 women with a median age of 50 years (range, 28 to 68 y). Three of the tumors were originally diagnosed as undifferentiated epithelioid or round cell malignant neoplasms; 1 tumor contained focal squamous differentiation and was originally diagnosed as a poorly differentiated squamous carcinoma of probable thymic origin. We find that the incidence of NMC within the mediastinum, particularly among undifferentiated tumors, is similar to that reported at other anatomic sites. NMC should be considered in the differential diagnosis of any poorly differentiated epithelioid mediastinal tumor, regardless of age.

Stathmin is involved in the cooperative effect of Zoledronic acid and gefitinib on bone homing breast cancer cells in vitro

Zoledronic acid (Zol) is the most potent inhibitor of bone resorption among the bisphosphonates and is commonly used for inhibiting bone metastasis. However, it remains unclear whether Zol provides a survival benefit. Recent findings indicate that epidermal growth factor (EGF) signaling is an important mediator of bone metastasis. Thus, we examined the combined effects of Zol and an EGF receptor-tyrosine kinase inhibitor, gefitinib, on the proliferation and invasion of a bone-seeking clone and the breast cancer cell line MDA-MB-231. Combined treatment with Zol and gefitinib synergistically inhibited both invasion and cell proliferation of the bone-seeking clone, but not those of the MDA-MB-231 cells. Two-dimensional difference gel electrophoresis and mass spectrometry demonstrated that stathmin was down-regulated during these cooperative effects. Stathmin is a signal transduction regulatory factor which plays an important role in cell division and malignant tumor development. Our data suggest that stathmin may be a promising target molecule for blocking bone metastasis of breast cancer.

Clinical analysis of 15 cases of malignant ovarian germ cell tumors with lung metastasis

To investigate the clinical characteristics, diagnosis, treatment and prognosis of malignant ovarian germ cell tumors (MOGCT) with lung metastasis. Fifteen patients of MOGCT with lung metastasis treated in Peking Union Medical College Hospital from Jan. 1982 to Dec. 2010 was retrospectively analyzed. (1) Clinical characteristics: the average onset age of these 15 patients is (23 ± 11) years old (6 - 48 years). The majority of these patients presented with abdominal pain (8/15) or irregular vaginal bleeding (4/15) as their initial symptoms. The primary tumor located in the left ovary in 8 cases, right ovary in 6 cases, and both sides in only 1 case. Metastatic lesions were confined to the lung in 12 patients, while the other 3 patients were found to have multi-site distant metastasis. (2) DIAGNOSIS:all 15 cases included 9 pure non-gestational ovarian choriocarcinoma (NGOC), 3 MOGCT containing choriocarcinoma component (one mature teratoma with choriocarcinoma component, one endodermal sinus tumor with embryonal carcinoma and choriocarcinoma components, one choriocarcinoma with dysgerminoma component), 2 embryonal carcinoma, one immature teratoma. Only one patient in these 15 cases was correctly diagnosed before surgery. (3) Time of lung metastasis:of 12 MOGCT with choriocarcinoma component, 11 patients were found to have lung metastasis in the course of their primary treatment, only 1 had lung metastasis 2 months after the synthetic treatment finished. Three MOGCT patients without choriocarcinoma component were all found to have lung metastasis when tumor relapsed in the advanced stages of the disease. (4) TREATMENT:all 15 patients received multi-agent chemotherapy combined with surgery. The mean courses of chemotherapy for these patients were 16 courses (5 - 43 courses). (5) PROGNOSIS: of these 15 cases, complete remission was obtained in 10 patients of NGOC or mixed ovarian germ cell tumors with choriocarcinoma component, 3 patients (one NGOC, one endodermal carcinoma and one immature teratoma, respectively) died in the course of treatment as result of tumor progression, 2 progressed cases (one NGOC and one endodermal carcinoma respectively) abandoning therapy were lost to follow up. MOGCT with lung metastasis are more often to found in NGOC patients. These patients could obtain high complete remission rate after standard multi-agent chemotherapy combined with surgery. The prognosis of MOGCT with lung metastasis containing choriocarcinoma component are better than that of those without containing choriocarcinoma component.

Correlation between glucose transporter type-1 expression and18F-FDG uptake on PET in oral cancer

Objectives: Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) is a non-invasive diagnostic tool for many human cancers wherein glucose uptake transporter-1 (GLUT-1) acts as a main transporter in the uptake of 18F-FDG in cancer cells. Increased expression of glucose transporter-1 has been reported in many human cancers. In this study, we investigated the correlation between 18F-FDG accumulation and expression of GLUT-1 in oral cancer. Materials and Methods: We evaluated 42 patients diagnosed with oral squamous cell carcinoma (OSCC) and malignant salivary gland tumor as confirmed by histology. 42 patients underwent pre-operative 18F-FDG PET, with the maximum standardized uptake value (SUVmax) measured in each case. Immunohistochemical staining was done for each histological specimen, and results were evaluated post-operatively according to the percentage (%) of positive area, intensity, and staining score. Results: For OSCC, SUVmax significantly increased as T stage of tumor classification increased. For malignant salivary gland tumor, SUVmax significantly increased as T stage of tumor classification increased. For OSCC, GLUT-1 was expressed in all 36 cases. GLUT-1 staining score (GSS) increased as T stage of tumor classification increased, with the difference statistically significant. For malignant salivary gland tumor, GLUT-1 expression was observed in all 6 cases; average GSS was significantly higher in patients with cervical lymph node metastasis than that in patients without cervical lymph node metastasis. Average GSS was higher in OSCC (11.11±1.75) than in malignant salivary gland tumor (5.33±3.50). No statistically significant correlation between GSS and SUVmax was observed in OSCC or in malignant salivary gland tumor. Conclusion: We found no statistically significant correlation between GSS and SUVmax in OSCC or in malignant salivary gland tumor. Studies on the various uses of GLUT during 18F-FDG uptake and SUV and GLUT as tumor prognosis factor need to be conducted through further investigation with large samples.

The treatment and prognosis of intracranial nongerminomatous malignant germ cell tumors in pineal region

Objective To investigate the clinical feature,treatment and prognosis of intracranial nongerminomatous malignant germ cell tumors (NGMGCTs) in pineal region.Methods Records of 34 such kind patients treated in our hospital between Jan 2000 and Jan 2010 were reviewed retrospectively.Clinical manifestations,diagnosis,treatment and outcome were analyzed in each patient.All tumors were microsurgically removed by occipital transtentorial approach (Poppen) and treated with radiotherapy combined chemotherapy.Results The tumor was totally removed in 32 cases,sub - totally in 2.In these 34 cases,all were verified by pathology,viz.11 immature teratomas,2 teratoma with malignant transformation,6 choriocarcinoma,2 embryonal carcinomas and 1 yolk sac tumors,12 mix germ cell tumors.Thirty - one patients were followed up.The overall 1 - year survival rate was 97％,3 - year survival rate 62％ and 5 -year survival rate 44％.Immature teratomas 1 - year survival rate was 100％,3 - year survival rate 67％.Teratoma with malignant transformation 1 - year survival rate was 100％,1 - year survival rate was 33％.Choriocarcinoma,embryonal carcinomas and yolk sac tumors 1 - year survival rate was 88％,3 - year survival rate 55％,5 - year survival rate 33％.Mix germ cell tumors 1 - year survival rate was 100％,3 -year survival rate 67％,5 - year survival rate 67％.Conclusion The majority of pineal region NGMGCTs can be diagnosed by clinical manifestations,imaging data and tumor markers pre - operatively Surgery remains the first choice for NGMGCT based on tumor histology.Combined regimen of surgical resection,radiotherapy and chemotherapy is mostly effective. Key words: Pineal region; Germ cell tumors; Prognosis; Treatment

Simultaneous Squamous Cell Carcinoma of Cervix and Fallopian Tube; A Case Report

We report a case of simultaneous Squamous cell carcinoma(SCC) of cervix and fallopian tube (invasive). Primary carcinoma of the fallopian tube is a rare neoplasm, accounting for only 0.3–1.1% of all gynecological malignancies [1]. Adeno-carcinoma is the predominant type and is included in the criteria established by Finn and Javert for diagnosis of primary carcinoma of fallopian tube [2]. Other cell types, including adeno-squamous, endometriod, and malignant mixed mullerian tumour, have also been reported [2].

Foxml research progress in cell cycle and tumor

Forkhead Box ml （ Foxml ） is a component of the Fox transcription factor family. It is only detected in proliferating ceils, but disappears when cells enter into their terminal differentiation phase. Foxml is closely related to cellular growth mainly through inhibiting cyclin-dependent kinase（cdk） inhibitors to influence cell proliferation. It also participates in growth hormone mediated cell multiplication. The overexpression of Foxml has been observed in many tumor cell lines and malignant tumors, indicating that Foxml might be an essential proto-oncogene in carcinoaenesis. Upregulation of Foxml is sufficient to induce genomic instability due to loss of heterozygosity and variation of copy numbers. Foxml-induced genomic instability was significantly enhanced and accumulated with increasing cell passages. Foxml might become a new potential target for the treatment human cancer based on future investigations. Key words: Neoplasms ; Cell cycle ; Transcription factors