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Subrata Deb, Steven Pham, Dong-Sheng Ming, Mei Yieng Chin, Hans Adomat, Antonio Hurtado-Coll, Martin E Gleave, Emma S Tomlinson Guns
Castration-resistant prostate tumors acquire the independent capacity to generate androgens by upregulating steroidogenic enzymes or using steroid precursors produced by the adrenal glands for continued growth and sustainability. The formation of steroids was measured by liquid chromatography-mass spectrometry in LNCaP and 22Rv1 prostate cancer cells, and in human prostate tissues, following incubation with steroid precursors (22-OH-cholesterol, pregnenolone, 17-OH-pregnenolone, progesterone, 17-OH-progesterone)...
September 20, 2018: Cancers
Babak Nami, Hamid Maadi, Zhixiang Wang
Human epidermal growth factor receptor (HER) 2 (HER2) is overexpressed in 20⁻30% of breast cancers. HER2 is a preferred target for treating HER2-positive breast cancer. Trastuzumab and pertuzumab are two HER2-targeted monoclonal antibodies approved by the Food and Drug Administration (FDA) to use as adjuvant therapy in combination with docetaxel to treat metastatic HER2-positive breast cancer. Adding the monoclonal antibodies to treatment regimen has changed the paradigm for treatment of HER2-positive breast cancer...
September 20, 2018: Cancers
Sonia Leon-Cabrera, Armando Vázquez-Sandoval, Emmanuel Molina-Guzman, Yael Delgado-Ramirez, Norma L Delgado-Buenrostro, Blanca E Callejas, Yolanda I Chirino, Carlos Pérez-Plasencia, Miriam Rodríguez-Sosa, Jonadab E Olguín, Citlaltepetl Salinas, Abhay R Satoskar, Luis I Terrazas
Signal transducer and activator of transcription 1 (STAT1) is part of the Janus kinase (JAK/STAT) signaling pathway that controls critical events in intestinal immune function related to innate and adaptive immunity. Recent studies have implicated STAT1 in tumor⁻stroma interactions, and its expression and activity are perturbed during colon cancer. However, the role of STAT1 during the initiation of inflammation-associated cancer is not clearly understood. To determine the role of STAT1 in colitis-associated colorectal cancer (CAC), we analyzed the tumor development and kinetics of cell recruitment in wild-type WT or STAT1-/- mice treated with azoxymethane (AOM) and dextran sodium sulfate (DSS)...
September 19, 2018: Cancers
Beatrice U Mueller, Katja Seipel, Ulrike Bacher, Thomas Pabst
While the majority of patients with acute myeloid leukemia (AML) are above the age of 65 years at diagnosis, the outcome of older AML patients remains disappointing. Even if standard intensive chemotherapy induces morphologic complete remission (CR1), relapses in older AML patients are common leading to poor long-term survival outcomes. Since autologous hematopoietic stem cell transplantation (HCT) offers distinct anti-leukemic effectiveness while avoiding graft-versus-host disease associated with allogeneic transplantation, it represents an option for consolidation treatment in selected older AML patients...
September 19, 2018: Cancers
Amruta P Nayak, Arvinder Kapur, Lisa Barroilhet, Manish S Patankar
Aerobic glycolysis is an important metabolic adaptation of cancer cells. There is growing evidence that oxidative phosphorylation is also an active metabolic pathway in many tumors, including in high grade serous ovarian cancer. Metastasized ovarian tumors use fatty acids for their energy needs. There is also evidence of ovarian cancer stem cells privileging oxidative phosphorylation (OXPHOS) for their metabolic needs. Metformin and thiazolidinediones such as rosiglitazone restrict tumor growth by inhibiting specific steps in the mitochondrial electron transport chain...
September 18, 2018: Cancers
Teresa Poggio, Justus Duyster, Anna L Illert
T cell non-Hodgkin lymphoma (T-NHL) is a rare and heterogeneous group of neoplasms of the lymphoid system. With the exception of a few relatively indolent entities, T-NHL is typically aggressive, treatment resistant, and associated with poor prognosis. Relatively few options with proven clinical benefit are available for patients with relapsed or refractory disease. Immunotherapy has emerged as a promising treatment for the management of patients with hematological malignancies. The identification of tumor antigens has provided a large number of potential targets...
September 18, 2018: Cancers
Tatsuya Ohno, Shin-Ei Noda, Kazutoshi Murata, Yuya Yoshimoto, Noriyuki Okonogi, Ken Ando, Tomoaki Tamaki, Shingo Kato, Takashi Hirakawa, Tatsuya Kanuma, Takashi Minegishi, Takashi Nakano
A phase I study was performed to determine the recommended dose of carbon ion radiotherapy and 3D image-guided brachytherapy for histologically confirmed stage II (≥4 cm), III, or IVA cervical cancer. Dose-limiting toxicities (treatment-related toxicities occurring within three months from the start of carbon ion radiotherapy) included Grade 3 non-hematological toxicity, Grade 4 hematological toxicity, or interruption of treatment for more than two weeks due to treatment-related toxicities. Carbon ion radiotherapy consisted of whole-pelvic irradiation with 36...
September 18, 2018: Cancers
Brigitte Bauvois, Santos A Susin
Human neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein present in a wide variety of tissues and cell types. NGAL exists as a 25 kDa monomer, a 46 kDa homodimer (the most abundant form in healthy subjects) and a 130 kDa disulfide-linked heterodimer bound to latent matrix metalloproteinase-9. Dysregulated expression of NGAL in human malignancies suggests its value as a clinical marker. A growing body of evidence is highlighting NGAL's paradoxical (i.e., both beneficial and detrimental) effects on cellular processes associated with tumor development (proliferation, survival, migration, invasion, and multidrug resistance)...
September 18, 2018: Cancers
Aleksandra Simiczyjew, Ewelina Dratkiewicz, Marleen Van Troys, Christophe Ampe, Ilona Styczeń, Dorota Nowak
Triple-negative breast cancer (TNBC) is the most challenging subtype to treat due to the lack of estrogen receptor, progesterone receptor, and HER2 expression, which excludes the usage of directed targeted therapy against them. Promising therapeutic targets are the hepatocyte growth factor receptor (MET) and epidermal growth factor receptor (EGFR), which expression is frequently elevated in TNBC. Inhibitors of these receptors used as monotherapy are often ineffective. Due to that, we studied the efficacy of combined therapy targeting MET and EGFR simultaneously...
September 17, 2018: Cancers
Saúl Álvarez-Teijeiro, Cristina García-Inclán, M Ángeles Villaronga, Pedro Casado, Francisco Hermida-Prado, Rocío Granda-Díaz, Juan P Rodrigo, Fernando Calvo, Nagore Del-Río-Ibisate, Alberto Gandarillas, Francisco Morís, Mario Hermsen, Pedro Cutillas, Juana M García-Pedrero
This study investigates for the first time the crosstalk between stromal fibroblasts and cancer stem cell (CSC) biology in head and neck squamous cell carcinomas (HNSCC), with the ultimate goal of identifying effective therapeutic targets. The effects of conditioned media from cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs) on the CSC phenotype were assessed by combining functional and expression analyses in HNSCC-derived cell lines. Further characterization of CAFs and NFs secretomes by mass spectrometry was followed by pharmacologic target inhibition...
September 17, 2018: Cancers
Hiromasa Endo, Kanako Takayama, Kenji Mitsudo, Tatsuya Nakamura, Ichiro Seto, Hisashi Yamaguchi, Takashi Ono, Motohisa Suzuki, Yusuke Azami, Hitoshi Wada, Masao Murakami, Iwai Tohnai
This study aimed to evaluate the therapeutic effect and toxicity of proton beam therapy in combination with intra-arterial infusion chemotherapy in patients with squamous cell carcinoma of the maxillary gingiva. Between December 2010 and March 2016, 30 patients with T4 squamous cell carcinoma of the maxillary gingiva were treated with radiotherapy and retrograde intra-arterial infusion chemotherapy using cisplatin (20⁻40 mg/m², 4⁻6 times). Radiotherapy was basically administered using boost proton beam therapy for primary tumor and neck lymph node tumors, following 36⁻40 Gy photon radiation therapy delivered to the prophylactic area, to a total dose of 70...
September 15, 2018: Cancers
Ina Nepstad, Kimberley Joanne Hatfield, Tor Henrik Anderson Tvedt, Håkon Reikvam, Øystein Bruserud
Clonal heterogeneity detected by karyotyping is a biomarker associated with adverse prognosis in acute myeloid leukemia (AML). Constitutive activation of the phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway is present in AML cells, and this pathway integrates signaling from several upstream receptors/mediators. We suggest that this pathway reflects biologically important clonal heterogeneity. We investigated constitutive PI3K-Akt-mTOR pathway activation in primary human AML cells derived from 114 patients, together with 18 pathway mediators...
September 14, 2018: Cancers
Isaac Jardin, Raquel Diez-Bello, Jose J Lopez, Pedro C Redondo, Ginés M Salido, Tarik Smani, Juan A Rosado
Transient receptor potential channels convey signaling information from a number of stimuli to a wide variety of cellular functions, mainly by inducing changes in cytosolic Ca2+ concentration. Different members of the TRPC, TRPM and TRPV subfamilies have been reported to play a role in tumorigenesis. Here we show that the estrogen receptor positive and triple negative breast cancer cell lines, MCF7 and MDA-MB-231, respectively, exhibit enhanced expression of the TRPC6 channel as compared to the non-tumoral MCF10A cell line...
September 14, 2018: Cancers
Jin Wang, Tianfang Wang, Yanfang Sun, Yuan Feng, William C Kisseberth, Carolyn J Henry, Irene Mok, Susan E Lana, Kevin Dobbin, Nicole Northrup, Elizabeth W Howerth, Shaying Zhao
Spontaneous tumors in pet dogs represent a valuable but undercharacterized cancer model. To better use this resource, we performed an initial global comparison between proliferative and invasive colorectal tumors from 20 canine cases, and evaluated their molecular homology to human colorectal cancer (CRC). First, proliferative canine tumors harbor overactivated WNT/β-catenin pathways and recurrent CTNNB1 (β-catenin) mutations S45F/P, D32Y and G34E. Invasive canine tumors harbor prominent fibroblast proliferation and overactivated stroma...
September 14, 2018: Cancers
Gian Marco Elisi, Matteo Santucci, Domenico D'Arca, Angela Lauriola, Gaetano Marverti, Lorena Losi, Laura Scalvini, Maria Laura Bolognesi, Marco Mor, Maria Paola Costi
Drug repurposing is a fast and consolidated approach for the research of new active compounds bypassing the long streamline of the drug discovery process. Several drugs in clinical practice have been reported for modulating the major Hippo pathway's terminal effectors, namely YAP (Yes1-associated protein), TAZ (transcriptional co-activator with PDZ-binding motif) and TEAD (transcriptional enhanced associate domains), which are directly involved in the regulation of cell growth and tissue homeostasis. Since this pathway is known to have many cross-talking phenomena with cell signaling pathways, many efforts have been made to understand its importance in oncology...
September 14, 2018: Cancers
Sameer Abdallah Dhayat, Max Michael Traeger, Jan Rehkaemper, Anda Jana Stroese, Konrad Steinestel, Eva Wardelmann, Iyad Kabar, Norbert Senninger
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma entities worldwide with early and rapid dissemination. Recently, we discussed the role of microRNAs as epigenetic regulators of Epithelial-to-Mesenchymal Transition (EMT) in PDAC. In this study, we investigated their value as diagnostic and prognostic markers in tissue and blood samples of 185 patients including PDAC, non-malignant pancreatic disorders, and age-matched healthy controls. Expression of the microRNA-200-family (microRNAs -141, -200a, -200b, -200c, -429) and microRNA-148a was significantly downregulated in tissue of PDAC Union internationale contre le cancer (UICC) Stage II...
September 13, 2018: Cancers
Loukik Arora, Alan Prem Kumar, Frank Arfuso, Wee Joo Chng, Gautam Sethi
Signal transducer and activator of transcription 3 (STAT3), a member of the STAT protein family, can be phosphorylated by receptor-associated Janus kinases (JAKs) in response to stimulation by cytokines and growth factors. It forms homo- or heterodimers that can translocate to the cell nucleus where they act as transcription activators. Constitutive activation of STAT3 has been found to be associated with initiation and progression of various cancers. It can exert proliferative as well as anti-apoptotic effects...
September 13, 2018: Cancers
Marius Ilié, Mélanie Beaulande, Saima Ben Hadj, Emmanuel Chamorey, Renaud Schiappa, Elodie Long-Mira, Sandra Lassalle, Catherine Butori, Charlotte Cohen, Sylvie Leroy, Olivier Guérin, Jérôme Mouroux, Charles-Hugo Marquette, Jean-François Pomerol, Gilles Erb, Véronique Hofman, Paul Hofman
With underrepresentation of elderly patients with lung adenocarcinoma (LADC) in anti-PD-1/PD-L1 clinical trials, better understanding of the interplay of PD-L1 and tumor-associated immune cells (TAICs) could assist clinicians in stratifying these patients for immunotherapy. One hundred and one patients with LADCs, stratified by age, were included for analysis of PD-L1 expression and density of TAICs expressing CD4, CD8, and CD33, by using multiplex chromogenic immunohistochemistry (IHC) assays and automated digital quantification...
September 13, 2018: Cancers
Elena Madrazo, David Ruano, Lorea Abad, Estefanía Alonso-Gómez, Carmen Sánchez-Valdepeñas, África González-Murillo, Manuel Ramírez, Javier Redondo-Muñoz
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. As ALL progresses, leukemic cells cross the endothelial barrier and infiltrate other tissues. Epigenetic enzymes represent novel therapeutic targets in hematological malignancies, and might contribute to cells' capacity to migrate across physical barriers. Although many molecules drive this process, the role of the nucleus and its components remain unclear. We report here, for the first time, that the expression of G9a (a histone methyltransferase related with gene silencing) correlates with the expression of the integrin subunit α4 in children with ALL...
September 12, 2018: Cancers
Jean-Paul Soulillou, Caner Süsal, Bernd Döhler, Gerhard Opelz
Because of a mutation of the gene allowing the synthesis of the Neu5Gc form of neuraminidic acid, humans lack the Neu5Gc present in other mammals and develop anti-Neu5Gc. However, humans can absorb dietary Neu5Gc and normal colon epithelium displays minute amounts of Neu5Gc. The potential "physiological" formation of in situ immune complexes has been proposed as a risk factor for colon cancer and as the link between red meat-rich diet and colon carcinoma. In this article, we took advantage of evidence that polyclonal rabbit IgG (ATG) elicits an immune response against Neu5Gc and we consulted a large data base of allograft recipients treated or not with animal-derived IgG to discuss this hypothesis...
September 12, 2018: Cancers
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