Although pancreatic cancer often invades peripancreatic adipose tissue, little information is known about cancer‐adipocyte interaction. We first investigated the ability of adipocytes to ...de‐differentiate to cancer‐associated adipocytes (CAAs) by co‐culturing with pancreatic cancer cells. We then examined the effects of CAA‐conditioned medium (CAA‐CM) on the malignant characteristics of cancer cells, the mechanism underlying those effects, and their clinical relevance in pancreatic cancer. When 3T3‐L1 adipocytes were co‐cultured with pancreatic cancer cells (PANC‐1) using the Transwell system, adipocytes lost their lipid droplets and changed morphologically to fibroblast‐like cells (CAA). Adipocyte‐specific marker mRNA levels significantly decreased but those of fibroblast‐specific markers appeared, characteristic findings of CAA, as revealed by real‐time PCR. When PANC‐1 cells were cultured with CAA‐CM, significantly higher migration/invasion capability, chemoresistance, and epithelial‐mesenchymal transition (EMT) properties were observed compared with control cells. To investigate the mechanism underlying these effects, we performed microarray analysis of PANC‐1 cells cultured with CAA‐CM and found a 78.5‐fold higher expression of SAA1 compared with control cells. When the SAA1 gene in PANC‐1 cells was knocked down with SAA1 siRNA, migration/invasion capability, chemoresistance, and EMT properties were significantly attenuated compared with control cells. Immunohistochemical analysis on human pancreatic cancer tissues revealed positive SAA1 expression in 46/61 (75.4%). Overall survival in the SAA1‐positive group was significantly shorter than in the SAA1‐negative group (P = .013). In conclusion, we demonstrated that pancreatic cancer cells induced de‐differentiation in adipocytes toward CAA, and that CAA promoted malignant characteristics of pancreatic cancer via SAA1 expression, suggesting that SAA1 is a novel therapeutic target in pancreatic cancer.
Cancer‐associated adipocyte (CAA) promotes migration/invasion of pancreatic cancer cells. CAA also induced pancreatic cancer cells drug resistance, epithelial‐mesenchymal transition.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The prostate is surrounded by periprostatic adipose tissue. Although adipose tissue was thought to play limited physiological roles, it has recently been recognized as an active endocrine organ, ...secreting growth factors and adipokines. Epidemiologically, obesity is associated with prostate cancer progression. A major mechanism to explain the link between obesity and cancer includes the insulin and insulin‐like growth factor (IGF)‐1 axis, sex steroids, and adipokines. When prostate cancer cells invade periprostatic adipose tissue, adipose tissue contributes to create the tumor microenvironment, mainly via adipokine secretion. Furthermore, direct crosstalk between adipocytes and cancer cells can exist. We showed that fatty acid‐binding protein 4 (FABP4) released from adipocytes was taken up into prostate cancer cells and may act as a carrier of an energy source for the invasion. Bone is an adipocyte‐rich organ and is the common metastatic site of prostate cancer. In the microenvironment of bone metastases, tumor cells, osteoblasts, osteoclasts, adipocytes, and other stromal cells are interacting with one another and organizing a complex system. Thus, growing evidence implicates adipose tissue as a critical contributor to the development of prostate cancer. A deeper understanding of the mechanisms leads to more effective therapeutic strategies for prostate cancer. J. Med. Invest. 65:9‐17, February, 2018
Purpose: Adenomatoid tumor is a rare benign genital tract neoplasm of mesothelial origin. Uterine adenomatoid tumors occur in the outer myometrium and may mimic leiomyomas. Because hormonal treatment ...is not applicable to adenomatoid tumors and laparoscopic enucleation is not easy as myomectomy, it is important to differentiate adenomatoid tumors from leiomyomas for the adequate treatment. The purpose of this study is to evaluate the MRI findings of adenomatoid tumor for the differentiation from leiomyoma.Methods: MRI findings of surgically proven 10 uterine adenomatoid tumors in 9 women were retrospectively evaluated with correlation to histopathological findings.Results: All 10 tumors appeared as solid myometrial masses and showed heterogeneous signal intensity with admixture of partially ill-defined slight high-intensity areas containing abundant tubular tumor cells and well-defined myoma-like low-intensity areas reflecting smooth muscle hypertrophy on T2WI including 4 lesions with peripheral ring-like high intensity. High-intensity areas on T2WI tended to show high intensity on diffusion-weighted imaging (DWI) with relatively high apparent diffusion coefficient (ADC), suggesting T2 shine-through effect due to abundant tubules. Intra-tumoral hemorrhage revealed on MRI was rare. Early intense contrast-enhanced areas on dynamic contrast-enhanced study were observed dominantly within the high-intensity areas but rarely within the low-intensity areas on T2WI.Conclusion: The outer myometrial mass with the admixture of well-defined low- and ill-defined high-intensity areas on T2WI may be suggestive of adenomatoid tumor. Peripheral ring-like high intensity on T2WI and DWI may also be suggestive. Dynamic contrast-enhanced MR study may be helpful for the differentiation from leiomyoma.
Aim
Polypoid endometriosis is a rare variant of endometriosis and may mimic malignancy. The purpose of this study is to evaluate magnetic resonance (MR) imaging characteristics of polypoid ...endometriosis for the differential diagnosis with malignancy.
Methods
MR imaging findings of four histologically proven polypoid endometriosis were retrospectively evaluated with the review of the literature.
Results
All polypoid endometriosis exhibited high signal intensity on T2‐weighted images reflecting abundant dilated endometrial glands. Peritoneal lesions were surrounded by low signal intensity rim represented the “black rim sign” reflecting endometriotic fibrous adhesion. Two cases arising from endometriotic cysts showed transmural extension (peritoneal extension and myometrial infiltration). Endometriotic hemorrhagic foci were demonstrated in four lesions as high signal intensity on T1‐weighted images and/or susceptibility‐induced signal voids on susceptibility‐weighted MR sequence. Diffusion‐weighted images showed high signal intensity with relatively high apparent diffusion coefficient (ADC) due to T2 shine‐through effect but no diffusion restriction, and dynamic contrast‐enhanced (DCE) MR imaging showed gradually increasing contrast‐enhancement pattern like benign pathologies.
Conclusions
Polypoid endometriosis may mimic malignancy; however, black rim sign may be a characteristic MR imaging finding for the peritoneal lesions, and no diffusion restriction and gradually increasing contrast‐enhancement pattern may reflect its benign nature.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The clinical outcomes of breast cancer patients treated with tamoxifen may be influenced by the activity of cytochrome P450 2D6 (CYP2D6) enzyme because tamixifen is metabolized by CYP2D6 to its ...active forms of antiestrogenic metabolite, 4‐hydroxytamoxifen and endoxifen. We investigated the predictive value of the CYP2D6*10 allele, which decreased CYP2D6 activity, for clinical outcomes of patients that received adjuvant tamoxifen monotherapy after surgical operation on breast cancer. Among 67 patients examined, those homozygous for the CYP2D6*10 alleles revealed a significantly higher incidence of recurrence within 10 years after the operation (P = 0.0057; odds ratio, 16.63; 95% confidence interval, 1.75–158.12), compared with those homozygous for the wild‐type CYP2D6*1 alleles. The elevated risk of recurrence seemed to be dependent on the number of CYP2D6*10 alleles (P = 0.0031 for trend). Cox proportional hazard analysis demonstrated that the CYP2D6 genotype and tumor size were independent factors affecting recurrence‐free survival. Patients with the CYP2D6*10/*10 genotype showed a significantly shorter recurrence‐free survival period (P = 0.036; adjusted hazard ratio, 10.04; 95% confidence interval, 1.17–86.27) compared to patients with CYP2D6*1/*1 after adjustment of other prognosis factors. The present study suggests that the CYP2D6 genotype should be considered when selecting adjuvant hormonal therapy for breast cancer patients. (Cancer Sci 2008; 99: 995–999)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A 66-year-old Japanese man receiving systemic chemotherapy for advanced gastric cancer presented with exertional dyspnea. D-dimer was elevated in the blood. Echocardiography revealed pulmonary ...hypertension, and a ventilation-perfusion scan indicated decreased perfusion in the bilateral lungs. Cardiac catheterization showed no evidence of pulmonary artery embolization and revealed cytologically confirmed adenocarcinoma. Thus, pulmonary tumor thrombotic microangiopathy (PTTM) was diagnosed. The patient died of respiratory failure on the 17th hospitalization day despite systemic chemotherapy. Retrospective serological testing revealed increased vascular endothelial growth factor in the pulmonary artery blood. This is a rare case with antemortem cytologically proven PTTM mediated by VEGF.
Aims
BCOR gene alteration is a genetic signature of rare subsets of sarcomas. Most BCOR‐associated sarcomas thus far reported are in the pediatric population, except for uterine sarcomas. We studied ...seven cases of BCOR‐associated non‐uterine sarcomas in adult patients.
Methods and results
The patients were four men and three women ranging from 26 to 71 years in age. Three tumors, two of which primarily affected the kidney, showed BCOR‐CCNB3. One tumor with a ZC3H7B‐BCOR occurred in the chest wall, and a tumor with a novel CIITA‐BCOR was found in the sinonasal tract. Two tumors in the lung and breast harbored exon 15 internal tandem duplications of BCOR, a highly unexpected observation in this age group. All seven sarcomas consisted of dense proliferations of uniform round to spindle cells with fine chromatin within vascular stroma. BCOR‐CCNB3 sarcomas showed swirling fascicular growth. The tumor with the ZC3H7B‐BCOR fusion showed a multinodular growth of spindle cells, and the tumors with the CIITA‐BCOR fusion showed palisading of oval cells. Both tumors with BCOR internal tandem duplication demonstrated nested to palisading growth of round cells within sclerotic non‐myxoid stroma. All seven sarcomas diffusely expressed BCOR and SATB2 immunohistochemically, with all three BCOR‐CCNB3 sarcomas being immunopositive for CCNB3. BCOR alterations were confirmed by RNA sequencing, polymerase chain reaction, Sanger sequencing, and/or fluorescence in situ hybridization.
Conclusions
This study expands the clinicopathologic and molecular spectrum of BCOR‐associated sarcomas, and emphasizes the importance of being aware of this entity in the differential diagnosis of adult non‐uterine sarcomas.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background
Recently, the evaluation of the tumor size and local extension of early-stage uterine cervical cancer on magnetic resonance imaging is important for the accurate clinical staging and to ...determine the indication of less extensive surgery such as fertility sparing radical trachelectomy.
Purpose
To compare the diagnostic ability of reduced field-of-view diffusion-weighted imaging with those of three-dimensional (3D) contrast-enhanced T1-weighted imaging and T2-weighted imaging for assessing the tumor margin delineation and local extent of uterine cervical cancer.
Material and Methods
3T magnetic resonance images, including T2-weighted imaging, reduced field-of-view diffusion-weighted imaging, and 3D contrast-enhanced T1-weighted imaging, in 27 women with surgically proven cervical cancer (19 FIGO stage IB1, 3 IB2, and 5 IIA1) were retrospectively evaluated. Tumor margins and local tumor extent, including the presence of invasion to parametrium and vagina were evaluated on both sagittal and oblique axial (short axis) images; the results were compared with histologically confirmed tumor extension.
Results
Reduced field-of-view diffusion-weighted imaging diagnosed the tumor margins, which was more accurate than T2-weighted imaging (P<0.001) and slightly better than 3D contrast-enhanced T1-weighted imaging. Reduced field-of-view diffusion-weighted imaging could define the tumor margins well even in small lesions (≤ 20 mm). Histological examination revealed parametrial invasion in two cases (clinically under-staged) and vaginal invasion in four cases. Reduced field-of-view diffusion-weighted imaging could demonstrate local extension of all lesions, which was more accurate than clinical examination and T2-weighted imaging.
Conclusion
Addition of reduced field-of-view diffusion-weighted imaging may improve the staging accuracy of magnetic resonance imaging for cervical cancer in assessing the local tumor extent.
JMJD2A sensitizes gastric cancer to chemotherapy by cooperating with CCDC8 Nakagawa, Tadahiko; Sato, Yasushi; Tanahashi, Toshihito ...
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association,
05/2020, Volume:
23, Issue:
3
Journal Article
Peer reviewed
Open access
Background
Jumonji domain-containing protein 2A (JMJD2A) of the JMJD2 family of histone lysine demethylases has been implicated in tumorigenesis. However, its expression and role in gastric cancer ...(GC) drug resistance remain unknown. Here, we investigated the role of JMJD2A in GC chemotherapeutic susceptibility and its clinical relevance in GC.
Methods
We selected 12 relevant genes from previously identified gene signatures that can predict GC susceptibility to docetaxel, cisplatin, and S-1 (DCS) therapy. Each gene was knocked down using siRNA in GC cell lines, and cell viability assays were performed. JMJD2A expression in GC cell lines and tissues was assessed using qRT-PCR and immunohistochemistry, respectively. A JMJD2A downstream target related to drug susceptibility was examined using whole-gene expression array and immunoprecipitation.
Results
Among the 12 candidate genes, down-regulation of JMJD2A showed the maximum effect on GC susceptibility to anti-cancer drugs and increased the IC
50
values for 5-FU, cisplatin, and docetaxel 15.3-, 2.7-, and 4.0-fold, respectively. JMJD2A was universally expressed in 12 GC cell lines, and its overexpression in GC tissue was positively correlated with tumor regression in 34 DCS-treated patients. A whole-gene expression array of JMJD2A-knockdown GC cells demonstrated a significant decrease in the expression of pro-apoptotic coiled-coil domain containing 8 (CCDC8), a downstream target of JMJD2A. Direct interaction between CCDC8 and JMJD2A was verified using immunoprecipitation. CCDC8 inhibition restored drug resistance to docetaxel, cisplatin, and S-1.
Conclusions
Our results indicate that JMJD2A is a novel epigenetic factor affecting GC chemotherapeutic susceptibility, and JMJD2A/CCDC8 is a potential GC therapeutic target.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose: Red degeneration of uterine leiomyoma (RDL) is a hemorrhagic infarction caused by peripheral venous thrombosis. The peripheral high-intensity rim on T1-weighted MRI is characteristic for ...RDL; however, it may not be observed at all the phases of RDL. Susceptibility-weighted MR sequences (SWS) have exquisite sensitivity to blood products, and we hypothesized that the low-intensity rim due to the T2* shortening effects of blood products may be more clearly demonstrated on SWS. The purpose of this study is to evaluate the capability of SWS for the diagnosis of RDL.Methods: Surgically proven 15 RDL, which showed suggestive MRI findings (high-intensity rim or entirely high signal intensity on T1-weighted imaging) were retrospectively evaluated. MRI was qualitatively evaluated for the presence of high-intensity rim around a mass on fat-saturated T1-weighted images, and low-intensity rim on T2-weighted images and on SWS (susceptibility-weighted imaging SWI or T2-star-weighted angiography SWAN).Results: The high-intensity rim on T1-weighted images, low-intensity rim on T2-weighted images and on SWS were observed in 47%, 47%, and 100% of RDL, respectively. The other 53% of lesions showed entirely high signal intensity on T1-weighted images. Pathological examination revealed coagulative necrosis in all 15 lesions.Conclusion: SWS may be helpful for the diagnosis of RDL by revealing characteristic peripheral low-intensity rim.
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