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Computational and Structural... 2020Synthetic lethality is thought to play an important role in anticancer therapies. Herein, to understand the potential distributions and relationships between synthetic...
Synthetic lethality is thought to play an important role in anticancer therapies. Herein, to understand the potential distributions and relationships between synthetic lethal interactions between genes, especially for pairs deriving from different sources, we performed an integrative analysis of genes at multiple molecular levels. Based on inter-species phylogenetic conservation of synthetic lethal interactions, gene pairs from yeast and humans were analyzed; a total of 37,588 candidate gene pairs containing 7,816 genes were collected. Of these, 49.74% of genes had 2-10 interactions, 22.93% were involved in hallmarks of cancer, and 21.61% were identified as core essential genes. Many genes were shown to have important biological roles via functional enrichment analysis, and 65 were identified as potentially crucial in the pathophysiology of cancer. Gene pairs with dysregulated expression patterns had higher prognostic values. Further screening based on mutation and expression levels showed that remaining gene pairs were mainly derived from human predicted or validated pairs, while most predicted pairs from yeast were filtered from analysis. Genes with synthetic lethality were further analyzed with their interactive microRNAs (miRNAs) at the isomiR level which have been widely studied as negatively regulatory molecules. The miRNA-mRNA interaction network revealed that many synthetic lethal genes contributed to the cell cycle (seven of 12 genes), cancer pathways (five of 12 genes), oocyte meiosis, the p53 signaling pathway, and hallmarks of cancer. Our study contributes to the understanding of synthetic lethal interactions and promotes the application of genetic interactions in further cancer precision medicine.
PubMed: 33240468
DOI: 10.1016/j.csbj.2020.10.015 -
Urology Case Reports Nov 2023Prostate papillary and cribriform ductal prostatic adenocarcinoma is a rare malignancy infrequently reported in the literature. We describe a case of rectally invasive...
Prostate papillary and cribriform ductal prostatic adenocarcinoma is a rare malignancy infrequently reported in the literature. We describe a case of rectally invasive prostate cystic adenocarcinoma and surgical extirpative management not requiring fecal or urinary diversion.
PubMed: 37942212
DOI: 10.1016/j.eucr.2023.102597 -
Chinese Medical Journal Jun 2016Ovarian cancer is the most common cause of gynecological cancer-associated death. Iatrogenic menopause might adversely affect the quality of life and health outcomes in...
BACKGROUND
Ovarian cancer is the most common cause of gynecological cancer-associated death. Iatrogenic menopause might adversely affect the quality of life and health outcomes in young female cancer survivors. We evaluated whether postoperative hormone replacement therapy (HRT) had a negative influence on the progression-free survival (PFS) of patients with papillary serous ovarian cancer (SOC).
METHODS
We retrospectively reviewed the medical records of patients with papillary SOC, treated from January 1980 to December 2009, who suffered from menopause with or without HRT. Clinical characteristics of patients were compared between the two groups (HRT and non-HRT). Blood samples were collected from all the participants to detect serum cancer antigen (CA) 125. Hazard ratios with 95% confidential intervals for each variable were calculated by univariable and multivariable conditional Logistic regression analyses.
RESULTS
Among 112 identified patients, 31 were HRT users and 81 were not. The two groups did not significantly differ in median age at diagnosis (t = 0.652, P = 0.513), International Federation of Gynecology and Obstetrics (FIGO) stage (χ2 = 0.565, P = 0.754), differentiation (χ2 = 1.728, P = 0.422), resection status (χ2 = 0.070, P = 0.791), relapse (χ2 = 0.109, P = 0.741), chemotherapy course (t = -1.079, P = 0.282), follow-up interval (t = 0.878, P = 0.382), or PFS (t = 0.580, P = 0.562). Median Kupperman score at the onset of HRT was 30.81 and 12.19 after the therapy (t = 3.302, P = 0.001). According to the analysis, the strongest independent variables in predicting PFS were FIGO stage and disease that was not optimally debulked.
CONCLUSIONS
Postoperative HRT is not a prognostic factor for PFS of patients with papillary SOC. However, multicenter studies are needed to verify and extend our findings.
Topics: Adult; CA-125 Antigen; Cystadenocarcinoma, Serous; Disease-Free Survival; Female; Hormone Replacement Therapy; Humans; Membrane Proteins; Middle Aged; Ovarian Neoplasms; Prognosis; Proportional Hazards Models; Retrospective Studies; Young Adult
PubMed: 27231169
DOI: 10.4103/0366-6999.182835 -
Computational and Structural... 2020Classical microRNA (miRNA) has been so far believed as a single sequence, but it indeed contains multiple miRNA isoforms (isomiR) with various sequences and expression...
Classical microRNA (miRNA) has been so far believed as a single sequence, but it indeed contains multiple miRNA isoforms (isomiR) with various sequences and expression patterns. It is not clear whether these diverse isomiRs have potential relationships and whether they contribute to miRNA:mRNA interactions. Here, we aimed to reveal the potential evolutionary and functional relationships of multiple isomiRs based on let-7 and miR-10 gene families that are prone to clustering together on chromosomes. Multiple isomiRs within gene families showed similar functions to their canonical miRNAs, indicating selection of the predominant sequence. IsomiRs containing novel seed regions showed increased/decreased biological function depending on whether they had more/less specific target mRNAs than their annotated seed. Few gene ontology(GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were shared among the target genes of the annotated seeds and the novel seeds. Various let-7 isomiRs with novel seed regions may cause opposing drug responses despite the fact that they are generated from the same miRNA locus and have highly similar sequences. IsomiRs, especially the dominant isomiRs with shifted seeds, may disturb the coding-non-coding RNA regulatory network. These findings provide insight into the multiple isomiRs and isomiR-mediated control of gene expression in the pathogenesis of cancer.
PubMed: 32542110
DOI: 10.1016/j.csbj.2020.05.001 -
International Journal of Molecular... Apr 2017Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a...
Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received intraperitoneal injections of melatonin (200 µg/100 g body weight/day) for 60 days. Melatonin-treated animals showed a significant reduction in OC size and microvessel density. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1 was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFβ1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and, notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC in an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy.
Topics: Alcohol Drinking; Animals; Antioxidants; Blotting, Western; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Ethanol; Female; Food Preferences; Immunohistochemistry; Injections, Intraperitoneal; Melatonin; Microscopy, Fluorescence; Neovascularization, Pathologic; Ovarian Neoplasms; Rats; Receptor, Melatonin, MT1; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1
PubMed: 28398226
DOI: 10.3390/ijms18040763 -
Porcine Health Management Apr 2021The present paper reviews the occurrence of neoplasms in swine and presents a case series of 56 tumors submitted to the Slaughterhouse Support Network (Servei de Suport...
BACKGROUND
The present paper reviews the occurrence of neoplasms in swine and presents a case series of 56 tumors submitted to the Slaughterhouse Support Network (Servei de Suport a Escorxadors [SESC] IRTA-CReSA]) from slaughtered pigs from 1998 to 2018 (April) in Catalonia (Spain). The aim of the study was to describe the spectrum of spontaneous neoplastic lesions found in slaughtered pigs and to compare the reported tumor cases with previous published data. Lymphoid neoplasms were characterized and classified using the WHO classification adapted for animals.
RESULTS
The most reported neoplasm during this period was lymphoma (28). Within lymphomas, the B-cell type was the most common, being the diffuse large B-cell lymphoma (15/28) the most represented subtype. Other submitted non-lymphoid neoplasms included melanoma (7), nephroblastoma (3), mast cell tumor (2), liposarcoma (2), osteochondromatosis (2), papillary cystadenocarcinoma (1), peripheral nerve sheath tumor (1), lymphoid leukemia (1), fibropapilloma (1), hemangiosarcoma (1), hepatoma (1), histiocytic sarcoma (1), pheochromocytoma (1) and osteosarcoma (1).
CONCLUSIONS
The existence of a well-established Slaughterhouse Support Network allowed the compilation of comprehensive data for further epidemiological and pathological studies, particularly about less commonly reported lesions in livestock such as neoplasms in pigs.
PubMed: 33827694
DOI: 10.1186/s40813-021-00207-0 -
Plastic and Reconstructive Surgery.... Apr 2017Low-grade cribriform cystadenocarcinoma (LGCCC) is a rare tumor of the salivary gland that most often arises from the parotid gland. A 51-year-old man developed a small...
Low-grade cribriform cystadenocarcinoma (LGCCC) is a rare tumor of the salivary gland that most often arises from the parotid gland. A 51-year-old man developed a small mass on the right parotid gland 5 years ago. A preoperative magnetic resonance image showed abnormal intensity, an atypical characteristic for such a tumor; therefore, the diagnosis was difficult. Thus, a superficial parotidectomy was performed as a total excisional biopsy to remove the tumor. Histopathological analyses revealed that the tumor was composed of a single cyst comprising cells containing mucosal fluid, with proliferation of large cells. Also, proliferation of the tumor epithelium showed a papillary cribriform pattern of proliferation with a partial ring form, and the tissue inside the tumor was replaced by a hematoma. Mild cellular atypia was observed. Immunostaining for S-100 was positive, and the Ki-67 ratio was <5%. These histopathological findings led to a diagnosis of LGCCC of the parotid gland. At 54 months after surgery, the patient has had no recurrence or facial palsy. LGCCC is a rare neoplasm of the salivary gland and is listed in the current World Health Organization classification (2005) as a variant of cystadenocarcinoma. This case suggests that a thorough preoperative examination can lead to better diagnosis of rare tumors, including LGCCC. Thus, if a plastic surgeon is to correctly diagnose and treat parotid grand tumors, including LGCCC, then a detailed preoperative examination, including imaging, a disease course review, a physical examination, and differential diagnosis, should be considered carefully.
PubMed: 28507867
DOI: 10.1097/GOX.0000000000001306 -
Annals of Coloproctology Oct 2015We report a case of colonic metastasis from ovarian cancer presented as an intraluminal fungating mass mimicking primary colon cancer 8 years after surgery for ovarian...
We report a case of colonic metastasis from ovarian cancer presented as an intraluminal fungating mass mimicking primary colon cancer 8 years after surgery for ovarian cancer. A 70-year-old woman presented with constipation. She had undergone an extended total abdominal hysterectomy with bilateral salpingo-oophorectomy for an ovarian papillary serous cystadenocarcinoma 8 years earlier. Colonoscopy showed a large fungating mass 10 cm from the anal verge that was suspected to be colorectal cancer. A computed tomography scan showed a bulky intraluminal fungating mass in the rectosigmoid junction. After a lower anterior resection and a pathologic diagnosis, a diagnosis of a papillary serous adenocarcinoma due to metastasis from an ovarian tumor was made for this patient.
PubMed: 26576399
DOI: 10.3393/ac.2015.31.5.198 -
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 -
Modern Pathology : An Official Journal... Oct 2014High-grade serous carcinomas of the uterine adnexa with BRCA1 deficiency (high-grade serous carcinomas-BRCA) have recently been described to demonstrate characteristic...
High-grade serous carcinomas of the uterine adnexa with BRCA1 deficiency (high-grade serous carcinomas-BRCA) have recently been described to demonstrate characteristic histopathological features. We hypothesize that metastatic high-grade serous carcinomas-BRCA cases exhibit characteristic morphological features as well. We studied 102 high-grade serous carcinomas with known BRCA1 and BRCA2 genotype from the archives of the Department of Pathology at Memorial Sloan-Kettering Cancer Center. The primary site morphological characteristics of these cases were reported previously; we now focus solely on tumor morphology in sites other than the uterine adnexa (ie, metastatic sites). The study group consisted of the following case types: 13 BRCA1 germline mutations; 5 BRCA1 somatic mutations; 10 BRCA1 promoter methylation; 4 BRCA2 germline mutations; 1 BRCA2 somatic mutation; 11 lacking BRCA1 or BRCA2 abnormality; 58 cases lacking BRCA1 or BRCA2 germline mutation. Two observers independently scored invasion patterns and microscopic tumor architecture while blinded to genotype. Concordance between observers and correlations between metastatic patterns and the following indices were studied: genotype, primary site tumor characteristics, and BRCA1 immunohistochemistry. Concordance between observers was excellent (κ values >0.9). All cases with BRCA1 or 2 abnormalities showed either pushing pattern metastases (76%) or infiltrative metastases composed only of micropapillae (24%). In contrast, all cases lacking BRCA1 or 2 abnormalities showed infiltrative metastases that contained combinations of papillary, glandular, and, rarely, cribriform and micropapillary architecture (P<0.0001 for comparison with pushing metastasis and P<0.001 for comparison with purely micropapillary architecture). Morphological assessment of metastatic carcinomas, a highly reproducible exercise, accurately correlated with BRCA1 status in every case, unlike morphological assessment of primary site adnexal high-grade serous carcinomas or BRCA1 immunohistochemistry. Metastatic high-grade serous carcinomas-BRCAs exhibit characteristic morphological features that appear more sensitive and specific for BRCA mutations than two other morphologically based prediction systems and should be easier to apply in practice. These findings should be validated prospectively in an independent cohort.
Topics: Cystadenocarcinoma, Serous; Fallopian Tube Neoplasms; Female; Genes, BRCA1; Genes, BRCA2; Humans; Neoplasm Grading; Neoplasm Invasiveness; Ovarian Neoplasms
PubMed: 24577588
DOI: 10.1038/modpathol.2013.237