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https://www.readbyqxmd.com/read/30336465/mechanism-for-the-decision-of-ovarian-surface-epithelial-stem-cells-to-undergo-neo-oogenesis-or-ovarian-tumorigenesis
#1
Jiao Xu, Tuochen Zheng, Wenli Hong, Haifeng Ye, Chuan Hu, Yuehui Zheng
The ovary is surrounded by a whitish layer of mesodermally derived ovarian surface epithelium (OSE) that lines the intraembryonic celom and comprises simple squamous to cuboidal to low pseudostratified columnar epithelial cells. Its integrity is maintained by simple desmosomes, incomplete tight junctions, several integrins and cadherins. Recent research has found that ovarian stem cells (OSCs) exist within the OSE and may be responsible for both neo-oogenesis and ovarian cancer during adult life. The factors determining whether OSCs undergo neo-oogenesis or ovarian cancer are of great interest to researchers and clinicians...
October 18, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30318086/specific-active-immunotherapy-with-the-hebersavax-vegf-based-cancer-vaccine-from-bench-to-bedside
#2
REVIEW
Yanelys Morera-Díaz, Jorge V Gavilondo, Mónica Bequet-Romero, Javier Sánchez Ramírez, Francisco Hernández-Bernal, Katty-Hind Selman-Housein, Lincidio Perez, Marta Ayala-Ávila
HEBERSaVax is a cancer therapeutic vaccine candidate based on the combination of a recombinant antigen representative of human vascular endothelial growth factor (VEGF), and clinically tested adjuvants. The vaccine has been shown to inhibit tumor growth and metastases in mice, and to induce VEGF-blocking antibodies and specific T-cell responses in several animal species, all with an excellent safety profile. After preclinical studies, two sequential phase 1 clinical trials were conducted with HEBERSaVax to assess safety, tolerance, and immunogenicity in patients with advanced solid tumors, at different antigen doses, and combined with two distinct adjuvants...
January 2018: Seminars in Oncology
https://www.readbyqxmd.com/read/30315273/targeted-next-generation-sequencing-of-endometrial-cancer-and-matched-circulating-tumor-dna-identification-of-plasma-based-tumor-associated-mutations-in-early-stage-patients
#3
Ana M Bolivar, Rajyalakshmi Luthra, Meenakshi Mehrotra, Wei Chen, Bedia A Barkoh, Peter Hu, Wei Zhang, Russell R Broaddus
There is currently no blood-based marker in routine use for endometrial cancer patients. Such a marker could potentially be used for early detection, but it could also help to track tumor recurrence following hysterectomy. This is important, as extra-vaginal recurrence of endometrial endometrioid adenocarcinoma is usually incurable. This proof-of-principle study was designed to determine if tumor-associated mutations could be detected in cell-free DNA from the peripheral blood of early and late stage endometrial endometrioid carcinoma patients...
October 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/30304095/importance-of-the-putative-furin-recognition-site-742rnrr745-for-antiangiogenic-sema3c-activity-in-vitro
#4
I Valiulyte, V Preitakaite, A Tamasauskas, A Kazlauskas
Angiogenesis is one of the key processes in the growth and development of tumors. Class-3 semaphorins (Sema3) are characterized as axon guidance factors involved in tumor angiogenesis by interacting with the vascular endothelial growth factor signaling pathway. Sema3 proteins convey their regulatory signals by binding to neuropilins and plexins receptors, which are located on the effector cell. These processes are regulated by furin endoproteinases that cleave RXRR motifs within the Sema, plexin-semaphorins-integrin, and C-terminal basic domains of Sema3 protein...
October 8, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/30292626/hydropic-leiomyoma-a-distinct-variant-of-leiomyoma-closely-related-to-hmga2-overexpression
#5
Brannan B Griffin, Yanli Ban, Xinyan Lu, Jian-Jun Wei
Hydropic leiomyoma (HLM) is a variant of uterine leiomyoma with characteristic features of zonal distributions of edema, increased vascularity, and tumor cells arranged in nodules or cords. Diagnostic difficulty and patient management are further complicated by a lack of studies and unknown cause of the disease. To study this tumor's nature, 24 HLM cases were selected for analysis of cyto-histologic features, immunohistochemical profile (HMGA2, FH, CD34, pAKT, p16, ER, SMA and Ki-67), and molecular alterations of HMGA2 by fluorescence in-situ hybridization (FISH) and MED12 mutations...
October 4, 2018: Human Pathology
https://www.readbyqxmd.com/read/30291344/identification-of-a-subset-of-microsatellite-stable-endometrial-carcinoma-with-high-pd-l1-and-cd8-lymphocytes
#6
Suzanne Crumley, Katherine Kurnit, Courtney Hudgens, Bryan Fellman, Michael T Tetzlaff, Russell Broaddus
Immune checkpoint blockade has emerged as an effective therapeutic strategy for patients with advanced cancer. Identification of biomarkers associated with treatment efficacy will help to select patients more likely to respond to this approach. High levels of microsatellite instability, tumor expression of PD-L1, high tumor mutation burden, and increased tumor-infiltrating lymphocytes have all been associated with response to checkpoint inhibitor blockade. The purpose of this study was to determine if a subset of microsatellite-stable endometrioid endometrial carcinomas have higher immune cell infiltrates and/or expression of PD-L1...
October 5, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/30274313/molecular-scoring-of-hepatocellular-carcinoma-for-predicting-metastatic-recurrence-and-requirements-of-systemic-chemotherapy
#7
Naoshi Nishida, Takafumi Nishimura, Toshimi Kaido, Kosuke Minaga, Kentaro Yamao, Ken Kamata, Mamoru Takenaka, Hiroshi Ida, Satoru Hagiwara, Yasunori Minami, Toshiharu Sakurai, Tomohiro Watanabe, Masatoshi Kudo
Hepatocellular carcinoma (HCC) causes one of the most frequent cancer-related deaths; an HCC subset shows rapid progression that affects survival. We clarify molecular features of aggressive HCC, and establish a molecular scoring system that predicts metastasis after curative treatment. In total, 125 HCCs were examined for TP53 , CTNNB1 , and TERT promoter mutation, methylation of 8 tumor suppressor genes, and 3 repetitive DNA sequences to estimate promoter hypermethylation and global hypomethylation. A fractional allelic loss (FAL) was calculated to represent chromosomal instability through microsatellite analysis...
September 29, 2018: Cancers
https://www.readbyqxmd.com/read/30263099/apatinib-based-targeted-therapy-against-pulmonary-sarcomatoid-carcinoma-a-case-report-and-literature-review
#8
Xiaofeng Li, Yueming He, Jinfeng Zhu, Hongxia Pang, Yongwei Lin, Jinyang Zheng
Sarcomatoid carcinoma is a rare malignancy characterized by a combination of epithelial and sarcoma or sarcoma-like components. In this study, we reported one case of pulmonary sarcomatoid carcinoma and evaluated the safety and efficacy of apatinib, a tyrosine kinase inhibitor selectively targeting vascular endothelial growth factor receptor 2, in treating this disease. The tumor mass was detected in the left lung of a 75-year-old man and showed positive immunostaining for cytokeratin (CK) 7, CK8, smooth muscle actin, CD31, and CD34...
September 14, 2018: Oncotarget
https://www.readbyqxmd.com/read/30260442/clinical-and-molecular-characteristics-may-alter-treatment-strategies-of-thyroid-malignancies-in-dicer1-syndrome
#9
Karin van der Tuin, Leanne de Kock, Eveline J Kamping, Sabine E Hannema, Marie-Jose M Pouwels, Marek Niedziela, Tom van Wezel, Frederik J Hes, Marjolijn C Jongmans, William D Foulkes, Hans Morreau
Context: The DICER1 syndrome is a rare, autosomal dominant inherited disorder that predisposes to a variety of cancerous and noncancerous tumors of mostly pediatric- and adolescent-onset, including differentiated thyroid carcinoma (DTC). DICER1-related DTC has been hypothesized to arise secondary to the increased prevalence of pre-malignant lesions, i.e. thyroid hyperplastic nodules. Objective: To determine somatic alterations in DICER1-associated differentiated thyroid cancer and to study patient outcomes...
September 26, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/30218756/usefulness-of-complementary-next-generation-sequencing-and-quantitative-immunohistochemistry-panels-for-predicting-brain-metastases-and-selecting-a-treatment-outcomes-of-non-small-cell-lung-cancer
#10
Juliana Machado-Rugolo, Alexandre Todorovic Fabro, Daniel Ascheri, Cecília Farhat, Alexandre Muxfeldt Ab'Saber, Vanessa Karen de Sá, Maria Aparecida Nagai, Teresa Takagaki, Ricardo Terra, Edwin Roger Parra, Vera Luiza Capelozzi
To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non-small cell lung cancer (NSCLC) who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma (SqCC), and large-cell carcinoma (LCC) were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors (VEGFs)...
September 12, 2018: Human Pathology
https://www.readbyqxmd.com/read/30217561/kras-targeting-antibody-synergizes-anti-cancer-activity-of-gemcitabine-against-pancreatic-cancer
#11
Yeo Wool Kang, Ji Eun Lee, Kyung Hee Jung, Mi Kwon Son, Seung-Min Shin, Soo Jung Kim, Zhenghuan Fang, Hong Hua Yan, Jung Hee Park, Boreum Han, Min Ji Cheon, Min Gyu Woo, Joo Han Lim, Yong-Sung Kim, Soon-Sun Hong
Pancreatic cancer exhibits an oncogenic KRAS mutation rate of ∼90%. Despite research and drug development efforts focused on KRAS, no targeted therapy has been clinically approved for the treatment of pancreatic cancer with KRAS mutation. Also, the efficacy of gemcitabine is poor due to rapidly acquired resistance. We developed RT11-i antibody, which directly targets the intracellularly activated GTP-bound form of oncogenic RAS mutants. Here, we investigated the combined effects of RT11-i and gemcitabine in vitro and in vivo, and the mechanism involved...
December 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/30216333/the-evolving-story-of-pterygium
#12
Alvin L Young, Di Cao, Wai Kit Chu, Tsz Kin Ng, Yolanda W Y Yip, Vishal Jhanji, Chi Pui Pang
Pterygium is a fibrovascular subepithelial growth of degenerative tissue over the limbus. It is a common condition worldwide that is especially prevalent in tropical countries within the "pterygium belt." Its exact etiology remains to be elucidated; however, it is strongly associated with exposure to ultraviolet light. The high expression levels of tumor protein p53 (TP53) observed in laboratory studies of pterygium seem to contradict the fast-growing nature of its clinical behavior, and TP53 mutations have been suggested...
November 2018: Cornea
https://www.readbyqxmd.com/read/30180809/upper-limb-muscle-overgrowth-with-hypoplasia-of-the-index-finger-a-new-over-growth-syndrome-caused-by-the-somatic-pik3ca-mutation-c-3140a-g
#13
Mohammad M Al-Qattan, Ali Hadadi, Abdullah M Al-Thunayan, Ahmed A Eldali, Mohammed A AlBalwi
BACKGROUND: Scientists have previously described an overgrowth syndrome in Saudi patients and named it 'Upper limb muscle overgrowth with hypoplasia of the index finger' syndrome. CASE PRESENTATION: We describe a new case and document that the syndrome is caused by the somatic PIK3CA mutation c.3140A>G, p.His1047Arg. We also recruited one of the previously reported cases and found the same somatic mutation in the affected muscles. A wider classification of 'PIK3CA-related pathology spectrum' is presented which includes cancer, benign skin lesions/tumors, Cowden syndrome, isolated vascular malformations and various overgrowth syndromes...
September 4, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/30166433/multiple-brain-developmental-venous-anomalies-as-a-marker-for-constitutional-mismatch-repair-deficiency-syndrome
#14
S I Shiran, L Ben-Sira, R Elhasid, J Roth, U Tabori, M Yalon, S Constantini, R Dvir
BACKGROUND AND PURPOSE: Biallelic constitutional mutations in DNA mismatch repair genes cause a distinct syndrome, constitutional mismatch repair deficiency syndrome (CMMRD), characterized by cancers from multiple organs, most commonly brain tumors, during childhood. Surveillance protocols include total and brain MR imaging among other modalities to enable early detection of tumors. Brain surveillance scans revealed prominent brain developmental venous anomalies (DVAs) in some patients...
August 30, 2018: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/30158362/glucocorticoid-resistance-syndrome-caused-by-a-novel-nr3c1-point-mutation
#15
Reem Al Argan, Avi Saskin, Ji Wei Yang, Maria Daniela D'Agostino, Juan Rivera
Glucocorticoid resistance syndrome (GRS) is a rare genetic disorder caused by inactivating mutations of the NR3C1 gene which encodes the glucocorticoid receptor. The phenotypic spectrum is broad but typically include symptoms of adrenal insufficiency, mineralocorticoid excess and hyperandrogenism. We report a new case associated with a novel NR3C1 mutation. A 55-year-old woman with lifelong history of low body weight, hyperandrogenism and anxiety was seen at the endocrine clinic after left adrenalectomy and salpingoophorectomy for lesions suspicious of ovarian cancer and adrenal metastasis...
August 30, 2018: Endocrine Journal
https://www.readbyqxmd.com/read/30139561/dna-profile-components-predict-malignant-outcomes-in-select-cases-of-intraductal-papillary-mucinous-neoplasm-with-negative-cytology
#16
Rachel E Simpson, Nathan J Cockerill, Michele T Yip-Schneider, Eugene P Ceppa, Michael G House, Nicholas J Zyromski, Attila Nakeeb, Mohammad A Al-Haddad, C Max Schmidt
BACKGROUND: Predicting malignancy in intraductal papillary mucinous neoplasm remains challenging. Integrated molecular pathology combines pancreatic fluid DNA and clinical factors into a malignant potential score. We sought to determine the utility of DNA components alone in predicting high-grade dysplasia/invasive disease. METHODS: We reviewed prospectively the records from 1,106 patients with intraductal papillary mucinous neoplasm. We excluded non-intraductal papillary mucinous neoplasm cases and cases with definitive malignant cytology...
August 20, 2018: Surgery
https://www.readbyqxmd.com/read/30078412/clinical-implications-of-clonal-hematopoiesis
#17
REVIEW
David P Steensma
Clonal hematopoiesis (CH)-an expansion of blood cells derived from a single hematopoietic stem cell-is a defining feature of hematologic cancers, but recently CH was also found to be a frequent consequence of aging. When aging-associated CH results from acquisition of a somatic mutation in a driver gene associated with leukemia, and this mutation is present at a variant allele frequency of at least 0.02 (2%) yet the patient does not meet World Health Organization diagnostic criteria for a hematologic neoplasm, this state is termed clonal hematopoiesis of indeterminate potential (CHIP)...
August 2018: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/30045273/corkscrew-retinal-vessels-and-retinal-arterial-macroaneurysm-in-a-patient-with-neurofibromatosis-type-1-a-case-report
#18
Jia Lu, Haiyan Liu, Lin Zhang, Lingjun Ma, Hongyan Zhou
RATIONALE: Neurofibromatosis type I (NF-1) is a multisystem autosomal dominant disease characterized by pigmentation and the growth of tumors along nerves in the skin, brain, and other parts of the body. It is caused by a mutation in the NF-1 tumor suppressor gene. NF-1 vascular disease is an important complication of the disease. PATIENT CONCERNS: The study reports a unique case of a patient with NF-1 with 2 simultaneous vascular abnormalities, involving tiny spiral venous changes (corkscrew retinal vessels) and retinal arterial macroaneurysms...
July 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/30044141/stabilization-of-p22phox-by-hypoxia-promotes-pulmonary-hypertension
#19
Zuwen Zhang, Benjamin Trautz, Damir Kračun, Frederick Vogel, Michael Weitnauer, Katharina Hochkogler, Andreas Petry, Agnes Görlach
AIMS: Hypoxia and reactive oxygen species (ROS) have been shown to play a role in the pathogenesis of pulmonary hypertension (PH), a potentially fatal disorder characterized by pulmonary vascular remodeling, elevated pulmonary arterial pressure, and right ventricular hypertrophy. However, how they are linked in the context of PH is not completely understood. We, therefore, investigated the role of the NADPH oxidase subunit p22phox in the response to hypoxia both in vitro and in vivo. RESULTS: We found that hypoxia decreased ubiquitinylation and proteasomal degradation of p22phox dependent on prolyl hydroxylases (PHDs) and the E3 ubiquitin ligase protein von Hippel Lindau (pVHL), which resulted in p22phox stabilization and accumulation...
October 18, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/30015588/non-small-cell-lung-cancer-with-resistance-to-egfr-tki-therapy-ct-characteristics-of-t790m-mutation-positive-cancer
#20
Hyun Jung Koo, Mi Young Kim, Sojung Park, Han Na Lee, Hwa Jung Kim, Jae Cheol Lee, Sang-We Kim, Dae Ho Lee, Chang-Min Choi
Purpose To evaluate the clinical and CT characteristics of T790M mutation-positive non-small cell lung cancer (NSCLC) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy failure. Materials and Methods A retrospective study of 304 patients with NSCLC who underwent rebiopsy after first-line EGFR-TKI therapy was conducted. Rebiopsy methods included CT- or fluoroscopy-guided lung biopsies (n = 105), endobronchial US- or bronchofibroscopy-guided biopsies (n = 66), pleural fluid analysis (n = 47), other solid organ biopsies (n = 43), US-guided axillary or supraclavicular lymph node biopsies (n = 31), and cerebrospinal fluid analysis (n = 12)...
October 2018: Radiology
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