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Asian Pacific Journal of Cancer... May 2018Objectives: To compare survival outcomes between endometrial cancer (EC) patients with diabetes who used metformin to those who did not use metformin. Materials and...
Objectives: To compare survival outcomes between endometrial cancer (EC) patients with diabetes who used metformin to those who did not use metformin. Materials and Methods: A retrospective cohort study was conducted of EC patients who were diabetes at the time of their cancer diagnosis and had been scheduled for elective surgery at Rajavithi Hospital between 1 January 2003 and 31 December 2013. The patients were excluded if they had type I diabetes mellitus and a history of other cancers. Results: Of 1,262 EC patients in the study period, there was 212 (16.8%) patients who met the inclusion criteria. Among them, 90 (42.5%) were non-metformin users and 122 (57.5%) were metformin users. With a median follow-up of 47 months, the 5-year overall survivals (76.4% vs 77.9%, p=0.959) and the 5-year progression-free survivals (92.6% vs 84.7%, p=0.091) did not significantly differ between the both groups. On Cox proportional-hazards regression analysis, independent prognostic factors for overall survival (OS) were FIGO stage, depth of myometrial invasion, and cervical involvement. Patients with non-endometrioid histology and advanced stage were found to have a significant effect on progression-free survival (PFS). However, metformin used did not predict either OS (HR, 0.99; 95%CI, 0.56-1.73; p=0.959) or PFS (HR, 2.19; 95%CI, 0.86-5.55; p=0.099). Conclusion: Overall, a significant effect of metformin on survival outcomes in EC patients with diabetes was not found in the current study. Larger studies with a prospective randomized control design are needed to clarify the benefit of metformin as a strategy for endometrial cancer prevention and treatment.
Topics: Adenocarcinoma, Clear Cell; Carcinoma, Papillary; Cystadenocarcinoma, Serous; Diabetes Mellitus, Type 2; Endometrial Neoplasms; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Survival Rate
PubMed: 29802690
DOI: 10.22034/APJCP.2018.19.5.1295 -
Tumour Biology : the Journal of the... May 2018SPAG9 is a novel tumor associated antigen, expressed in variety of malignancies. However, its role in ovarian cancer remains unexplored. SPAG9 expression was validated...
SPAG9 is a novel tumor associated antigen, expressed in variety of malignancies. However, its role in ovarian cancer remains unexplored. SPAG9 expression was validated in ovarian cancer cells by real time PCR and Western blot. SPAG9 involvement in cell cycle, DNA damage, apoptosis, paclitaxel sensitivity and epithelial- mesenchymal transition (EMT) was investigated employing RNA interference approach. Combinatorial effect of SPAG9 ablation and paclitaxel treatment was evaluated in in vitro. Quantitative PCR and Western blot analysis revealed SPAG9 expression in A10, SKOV-3 and Caov3 compared to normal ovarian epithelial cells. SPAG9 ablation resulted in reduced cellular proliferation, colony forming ability and enhanced cytotoxicity of chemotherapeutic agent paclitaxel. Effect of ablation of SPAG9 on cell cycle revealed S phase arrest and showed decreased expression of CDK1, CDK2, CDK4, CDK6, cyclin B1, cyclin D1, cyclin E and increased expression of tumor suppressor p21. Ablation of SPAG9 also resulted in increased apoptosis with increased expression of various pro- apoptotic molecules including BAD, BID, PUMA, caspase 3, caspase 7, caspase 8 and cytochrome C. Decreased expression of mesenchymal markers and increased expression of epithelial markers was found in SPAG9 ablated cells. Combinatorial effect of SPAG9 ablation and paclitaxel treatment was evaluated in in vitro assays which showed that ablation of SPAG9 resulted in increased paclitaxel sensitivity and caused enhanced cell death. In vivo ovarian cancer xenograft studies showed that ablation of SPAG9 resulted in significant reduction in tumor growth. Present study revealed therapeutic potential of SPAG9 in ovarian cancer.
Topics: Adaptor Proteins, Signal Transducing; Adenocarcinoma; Adenocarcinoma, Papillary; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Cycle; Cell Cycle Checkpoints; Cell Line, Tumor; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Drug Resistance, Neoplasm; Drug Synergism; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Genetic Vectors; Humans; Injections, Intralesional; Mice, Nude; Molecular Targeted Therapy; Neoplasm Proteins; Ovarian Neoplasms; Paclitaxel; RNA Interference; RNA, Messenger; RNA, Neoplasm; RNA, Small Interfering; Tumor Stem Cell Assay; Xenograft Model Antitumor Assays
PubMed: 29745297
DOI: 10.1177/1010428318773652 -
The American Journal of Case Reports May 2018BACKGROUND There is now evidence to support that some cases of high-grade serous papillary carcinoma arise from the fallopian tubes rather than the ovaries. Common... (Review)
Review
BACKGROUND There is now evidence to support that some cases of high-grade serous papillary carcinoma arise from the fallopian tubes rather than the ovaries. Common symptoms at presentation include abdominal pain and swelling, vomiting, altered bowel habit and urinary symptoms. To our knowledge, this is the first case of serous papillary carcinoma presenting as a vaginal mass lesion. CASE REPORT A 41-year-old woman was referred to the Bnai-Zion Medical Center with the main complaint of irregular vaginal bleeding, vaginal mucous discharge, and suspected pelvic mass. Physical examination showed a soft, painless mass, measuring about 10 cm in diameter located mainly in the recto-vaginal septum, but not involving the uterus. Ultrasound examination showed no abnormal ovarian or uterine findings. Transvaginal biopsies of the mass showed a poorly differentiated serous papillary carcinoma of ovarian, tubal, or peritoneal origin. The physical examination and imaging findings strongly indicated an inoperable tumor, and the patient was treated with neoadjuvant (pre-surgical) chemotherapy. Pre-operative computed tomography (CT) imaging showed the partial involvement of the colon, and so surgical treatment included total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, partial vaginectomy, anterior rectal resection, and lymph node dissection. Histopathology of the surgical specimens showed a poorly differentiated serous carcinoma originating from the fimbria of the right fallopian tube. CONCLUSIONS To the best of our knowledge, this is the first report to describe primary fallopian tube papillary serous carcinoma presenting as a vaginal mass. Therefore, physicians should be aware of this possible diagnosis.
Topics: Adult; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Fallopian Tubes; Female; Genital Neoplasms, Female; Humans; Uterine Hemorrhage
PubMed: 29731507
DOI: 10.12659/AJCR.907444 -
Head and Neck Pathology Jun 2019DOG1 is an established diagnostic marker for gastrointestinal stromal tumours (GIST), but has been reported in salivary gland tumours (SGT) as an acinar and intercalated... (Comparative Study)
Comparative Study
DOG1 is an established diagnostic marker for gastrointestinal stromal tumours (GIST), but has been reported in salivary gland tumours (SGT) as an acinar and intercalated duct marker. However, its specificity and distribution is not well established. The aim of this study was to evaluate the diagnostic utility of DOG-1 expression in SGT in addition to comparing it with myoepithelial markers. Normal salivary tissue and SGT (n = 184) were examined for expression of DOG1 and a range of myoepithelial markers. SGT included: acinic cell carcinoma (ACC, n = 15), secretory carcinoma (SC, n = 9), pleomorphic adenoma (PA, n = 49), carcinoma ex-PA (Ca ex-PA, n = 11), adenoid cystic carcinoma (AdCC, n = 20), polymorphous adenocarcinoma (PAC, n = 6), myoepithelioma (n = 6), myoepithelial carcinoma (MC, n = 2), basal cell adenoma (BCA, n = 14), canalicular adenoma (CA, n = 19), mucoepidermoid carcinoma (MEC, n = 11), oncocytoma (n = 2), adenocarcinoma NOS (AdNOS, n = 4), basal cell adenocarcinoma (BCAC, n = 2), salivary duct carcinoma (SDC, n = 3) and papillary cystadenocarcinoma (PCAC, n = 1). Normal acini and ACC (14/15) showed strong luminal DOG1 staining; SC were largely negative with only focal expression in 3/9 cases. Luminal staining was seen in PA (14/49), PAC (4/6), Ca ex-PA (4/11) and AdCC (6/20). 8/11 MEC showed luminal and/or mucous cell staining. No staining was seen in myoepithelioma, MC, CA, adNOS and BCAC. BCA showed strong staining of myoepithelial cells in some cases (5/14). Variable myoepithelial DOG1 staining was seen in PA, Ca ex PA, BCA, SDC and PCAC which was not as consistent as myoepithelial markers such as calponin, p63 and αSMA. Absence of DOG1 can differentiate ACC from SC, but staining is variable in PA, PLGA and Ca ex-PA. Myoepithelial staining in some tumours but not in normal gland suggests a wider distribution in SGT than originally envisaged.
Topics: Anoctamin-1; Biomarkers, Tumor; Humans; Neoplasm Proteins; Salivary Gland Neoplasms
PubMed: 29671211
DOI: 10.1007/s12105-018-0917-3 -
International Journal of Clinical and... 2018Neuritin (Nrn1) is a glycophosphatidylinositol-linked protein that can be induced by neural activity in the central nervous system. However, its expression outside the...
OBJECTIVE(S)
Neuritin (Nrn1) is a glycophosphatidylinositol-linked protein that can be induced by neural activity in the central nervous system. However, its expression outside the nervous system and association with human cancers is unclear. This study investigated the expression of Nrn1 in human tissues as well as its association with human cancers.
MATERIALS AND METHODS
Nrn1 gene expression in human adult tissues was evaluated with the Clontech Multiple Tissue cDNA panel. Nrn1 protein in various tissues was detected by immunohistochemistry. Signal v.4.0 and TMHMM v.2.0 software were used to identify the signal peptide and transmembrane helix of Nrn1. The subcellular localization of Nrn1 in cultured SH-SY5Y cells was assessed by immunocytochemistry and western blotting. The expression of Nrn1 in human cancers were assessed using the online tools GEPIA.
RESULTS
Nrn1 mRNA was expressed in various tissues, compared to mRNA levels in the brain tissues, expression was high in the placenta, lungs, skeletal muscle, thymus, pancreas, liver and the heart tissues; lower levels were detected in the small intestine, ovary, spleen, and testes, but there was no detectable expression in the kidneys, colon, prostate or leukocytes. In SY5Y cells, Nrn1 was colocalized with caveolin 1 at the plasma membrane. Nrn1 was downregulated in Bladder Urothelial Carcinoma (BLCA); Breast invasive carcinoma (BRCA); Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC); Colon adenocarcinoma (COAD); Glioblastoma multiforme (GBM); Kidney Chromophobe (KIHC); Kidney renal papillary cell carcinoma (KIRP); Lower Grade GLioma (LGG); Rectum adenocarcinoma (READ); Uterine Corpus Endometrial Carcinoma (UCEC); Lung adenocarcinoma (LUA), Ovarian serous cystadenocarcinoma (OV) and upregulated in Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC). A combination of the overall survival analysis of the 12 kinds of human tumors with Nrn1 downregulation revealed that patients with high levels of Nrn1 present a long term survival. But there is no significant effect on DLBC patients' survival.
CONCLUSION
Nrn1 is expressed in various human tissues including the nervous system, specifically in the lipid rafts of cell membranes. We also provided the strong evidence that Nrn1 is associated with 13 kinds of human cancers and could function as biomarkers and therapeutic targets for these cancers.
PubMed: 31938301
DOI: No ID Found -
Molecular and Clinical Oncology Jan 2018Ovarian malignancies are rare in pregnancy; however, the incidence of abnormal adnexal masses diagnosed during pregnancy is increasing. The most common masses are...
Ovarian malignancies are rare in pregnancy; however, the incidence of abnormal adnexal masses diagnosed during pregnancy is increasing. The most common masses are ovarian cysts, and only 3-6% of those are malignant. The majority of ovarian masses are diagnosed at an early stage by routine ultrasound examinations. Malignant germ cell tumors are the most common ovarian malignancies associated with pregnancy, while the incidence of epithelial ovarian cancer is only 1:12,000-1:50,000 of pregnancies. The diagnosis and management of ovarian cancer during pregnancy remain unclear due to the rare occurrence and scant data on this condition. We herein report the case of 23-year-old woman with an extremely large ovarian papillary mucinous cystadenocarcinoma diagnosed during pregnancy, identified on ultrasound and magnetic resonance imaging, and treated by surgical resection followed by adjuvant chemotherapy with carboplatin and paclitaxel.
PubMed: 29399351
DOI: 10.3892/mco.2017.1501 -
Journal of Ovarian Research Jan 2018Toll-like receptors (TLRs) are transmembrane proteins expressed on the surface of ovarian cancer (OC) and immune cells. Identifying the specific roles of the...
BACKGROUND
Toll-like receptors (TLRs) are transmembrane proteins expressed on the surface of ovarian cancer (OC) and immune cells. Identifying the specific roles of the TLR-mediated signaling pathways in OC cells is important to guide new treatments. Because immunotherapies have emerged as the adjuvant treatment for patients with OC, we investigated the effect of a promising immunotherapeutic strategy based on protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) combined with cisplatin (CIS) on the TLR2 and TLR4 signaling pathways via myeloid differentiation factor 88 (MyD88) and TLR-associated activator of interferon (TRIF) in an in vivo model of OC.
METHODS
Tumors were chemically induced by a single injection of 100 μg of 7,12-dimethylbenz(a)anthracene (DMBA) directly under the left ovarian bursa in Fischer 344 rats. After the rats developed serous papillary OC, they were given P-MAPA, CIS or the combination P-MAPA+CIS as therapies. To understand the effects of the treatments, we assessed the tumor size, histopathology, and the TLR2- and TLR4-mediated inflammatory responses.
RESULTS
Although CIS therapy was more effective than P-MAPA in reducing the tumor size, P-MAPA immunotherapy significantly increased the expressions of TLR2 and TLR4. More importantly, the combination of P-MAPA with CIS showed a greater survival rate compared to CIS alone, and exhibited a significant reduction in tumor volume compared to P-MAPA alone. The combination therapy also promoted the increase in the levels of the following OC-related proteins: TLR4, MyD88, TRIF, inhibitor of phosphorylated NF-kB alpha (p-IkBα), and nuclear factor kappa B (NF-kB p65) in both cytoplasmic and nuclear sites. While P-MAPA had no apparent effect on tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6, it seems to increase interferon-γ (IFN-γ), which may induce the Thelper (Th1)-mediated immune response.
CONCLUSION
Collectively, our results suggest that P-MAPA immunotherapy combined with cisplatin could be considered an important therapeutic strategy against OC cells based on signaling pathways activated by TLR4.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Cell Line, Tumor; Cisplatin; Cystadenocarcinoma, Serous; Cytokines; Disease Models, Animal; Female; Humans; Immunohistochemistry; Linoleic Acids; NF-kappa B; Neoplasm Grading; Organophosphorus Compounds; Ovarian Neoplasms; Rats; Signal Transduction; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 29343281
DOI: 10.1186/s13048-018-0380-5 -
Journal of Ovarian Research Jan 2018Serous borderline tumor (SBT) of the micropapillary type (SBT-MP) became one of the major pathological SBT diagnoses in addition to typical SBT, and was also defined as...
MRI appearance of ovarian serous borderline tumors of the micropapillary type compared to that of typical ovarian serous borderline tumors: radiologic-pathologic correlation.
BACKGROUND
Serous borderline tumor (SBT) of the micropapillary type (SBT-MP) became one of the major pathological SBT diagnoses in addition to typical SBT, and was also defined as "non-invasive" low-gradeserous carcinoma according to the World Health Organization (WHO) classification in 2014. In this study, we investigated the MRI appearance of SBT-MP compared to that of typical SBT in order to identify specific imaging features of SBT-MP that correspond to pathological findings.
METHODS
MR images of 6 histologically proven ovarian SBT-MP in four patients and 14 typical SBT in ten patients were reviewed retrospectively. Images were evaluated for laterality, size and morphology of the lesion and the solid component (SC) and signal intensity (SI) of the SC. MRI findings were correlated with pathological findings.
RESULTS
The patients with SBT-MP (mean 26.3 years) were younger than those with typical SBT (mean 44.5 years). Postoperative staging in patients with SBT-MP was II in two and III in two cases, while staging for typical SBT was I in seven, II in one and III in two cases. The morphologic patterns of SBT-MP were a unilateral cystic mass with intracystic mural nodules (CwMN) (n = 2), bilateral solid papillary masses (SM), and bilateral SM with CwMN. The pattern of typical SBT was CwMN (n = 13) in all but one lesion (SM with CwMN). All SCs showed inhomogeneous slight hyperintensity on T2 weighted images (WI) and high SI on diffusion-WI (DWI) except for in one typical SBT. Although diffuse proliferation of the tumor cells in micropapillary projections with little stroma seemed to correspond to inhomogeneous slightly hyperintense foci in SC on T2WI and high SI on DWI, similar MR findings were observed in typical SBT in all lesions on T2WI and 11 of 12 lesions on DWI. In typical SBT, inhomogeneous slightly hyperintense foci in SC on T2WI and high SI on DWI corresponded to highly cellular foci with densely branched papillae.
CONCLUSION
Pathological findings and clinical behavior of SBT-MP differed from those of typical SBT, but morphology and SI of SC on MRI were similar, with papillary projections demonstrating inhomogeneous slight hyperintensity on T2WI and high SI on DWI.
Topics: Adult; Aged; Cystadenocarcinoma, Serous; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Middle Aged; Neoplasm Grading; Neoplasm Staging; Ovarian Neoplasms; Tumor Burden
PubMed: 29321056
DOI: 10.1186/s13048-018-0379-y -
Annals of Hepato-biliary-pancreatic... Nov 2017Mucinous tumors of the pancreas are rare and the diagnosis of invasive carcinoma can be a dilemma. While metastatic disease from mucinous cystadenocarcinoma (MCAC) and...
Mucinous tumors of the pancreas are rare and the diagnosis of invasive carcinoma can be a dilemma. While metastatic disease from mucinous cystadenocarcinoma (MCAC) and invasive intraductal papillary mucinous neoplasms (IPMN) have been reported, no extraperitoneal mucinous cystic metastatic disease has been described. When metastatic, the overall survival rates for invasive adenocarcinoma, mucinous cystadenocarcinoma (MCAC) and invasive intraductal papillary mucinous neoplasms (IPMN) are similar. The best improvement in the overall and progression free survival has been demonstrated with FOLFIRINOX (folinic acid - fluorouracil - irinotecan - oxaliplatin) for metastatic adenocarcinoma and Gemcitabine based regimens for MCAC. However, the variable responses of metastatic mucinous lesions have been observed and the overall prognosis remains poor. We describe a case of a patient who presented with metastatic adenocarcinoma of the pancreas as cystic masses in the supraclavicular and axillary regions. Additionally, this patient was initially treated with FOLFIRINOX and continues to have stable primary and metastatic disease after 18 months from the diagnosis.
PubMed: 29264591
DOI: 10.14701/ahbps.2017.21.4.247 -
Journal of Oral Biology and... 2017A 68-year-old Caucasian gentleman presented with a 6-month history of a left sided Level I/II neck swelling involving the floor of mouth. MRI revealed a large cystic...
A 68-year-old Caucasian gentleman presented with a 6-month history of a left sided Level I/II neck swelling involving the floor of mouth. MRI revealed a large cystic lesion and histology confirmed a diagnosis of primary papillary cystadenocarcinoma of the sublingual gland. Papillary cystadenocarcinoma was first described in 1991 by the World Health Organisation [WHO], and is a rare malignant neoplasm characterised by cysts and papillary endo-cystic projections. Papillary cystadenocarcinoma arising from the sublingual glands is extremely rare and has the potential to metastasise to cervical lymph nodes. This patient we report was therefore treated with surgical excision and post-operative radiotherapy.
PubMed: 29124004
DOI: 10.1016/j.jobcr.2017.03.003