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Novel therapies emerging in oncology to target the TGF-β pathway.

The TGF-β signaling pathway governs key cellular processes under physiologic conditions and is deregulated in many pathologies, including cancer. TGF-β is a multifunctional cytokine that acts in a cell- and context-dependent manner as a tumor promoter or tumor suppressor. As a tumor promoter, the TGF-β pathway enhances cell proliferation, migratory invasion, metastatic spread within the tumor microenvironment and suppresses immunosurveillance. Collectively, the pleiotropic nature of TGF-β signaling contributes to drug resistance, tumor escape and undermines clinical response to therapy. Based

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… recruiting NCT03802084 Vactosertib Imatinib TGF-β RI BCR-abl Advanced desmoid tumor 24 Ib/IIa Active recruiting NCT02452008 Galunisertib + Enzalutamide TGF-β RI AR Castration-resistant prostate cancer 60 II Active, recruiting NCT03206177 Galunisertib + Carboplatin/ Paclitaxel TGF-β RI Chemotherapy Ovarian carcinosarcoma … Imatinib | TGF-β RI BCR-abl | Advanced desmoid tumor | 24 | Ib/IIa | Active recruiting NCT02452008 | Galunisertib + Enzalutamide | TGF-β RI AR | Castration-resistant prostate cancer | 60 | II | Active, recruiting NCT03206177 | Galunisertib + Carboplatin/ Paclitaxel | TGF-β RI Chemotherapy | Ovarian carcinosarcoma …

33rd Европейский конгресс патологии - резюме.

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Engaging natural killer cells for cancer therapy via NKG2D, CD16A and other receptors.

The field of immuno-oncology has revolutionized cancer patient care and improved survival and quality of life for patients. Much of the focus in the field has been on exploiting the power of the adaptive immune response through therapeutic targeting of T cells. While these approaches have markedly advanced the field, some challenges remain, and the clinical benefit of T cell therapies does not extend to all patients or tumor indications. Alternative strategies, such as engaging the innate immune system, have become an intense area of focus in the field. In particular, the engagement of natural

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… large B-cell lymphoma, THYM: thymoma, LAML: acute myeloid leukaemia, UVM: uveal melanoma, PRAD: prostate adenocarcinoma, KICH: kidney chromophobe, LGG: brain lower grade glioma, LIHC: liver hepatocellular carcinoma, SKCM: skin cutaneous melanoma, PCPG: pheochromocytoma and paraganglioma, UCS: Uterine carcinosarcoma … large B-cell lymphoma, THYM: thymoma, LAML: acute myeloid leukaemia, UVM: uveal melanoma, PRAD: prostate adenocarcinoma, KICH: kidney chromophobe, LGG: brain lower grade glioma, LIHC: liver hepatocellular carcinoma, SKCM: skin cutaneous melanoma, PCPG: pheochromocytoma and paraganglioma, UCS: Uterine carcinosarcoma …

BREAST

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Role of PARP Inhibitors in Cancer Immunotherapy: Potential Friends to Immune Activating Molecules and Foes to Immune Checkpoints.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) induce cytotoxic effects as single agents in tumors characterized by defective repair of DNA double-strand breaks deriving from BRCA1/2 mutations or other abnormalities in genes associated with homologous recombination. Preclinical studies have shown that PARPi-induced DNA damage may affect the tumor immune microenvironment and immune-mediated anti-tumor response through several mechanisms. In particular, increased DNA damage has been shown to induce the activation of type I interferon pathway and up-regulation of PD-L1 expression in cance

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… niraparib plus/minus atezolizumab following platinum-based chemotherapy plus/minus atezolizumabin in recurrent ovarian, tubal or peritoneal cancer | NCT03598270 [ 298 ] niraparib | dostarlimab (anti PD-1) | ROCSAN | Niraparib plus dostarlimab and niraparib alone vs. chemotherapy in recurrent ovarian carcinosarcoma … In particular, ROCSAN is a multicenter, randomized, open-label, integrated phase 2/3 study comparing the efficacy of niraparib or niraparib plus dostarlimab vs. chemotherapy for the treatment of endometrial/ovarian carcinosarcoma after at least one line of platinum-based chemotherapy [ 299 ]. …

Резюме: 32 Второй Конгресс ЭСП и Международный конгресс XXXIII МПД.

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Artificial Neural Network Prediction of Mortality in Cancer Patients Presenting for Radiation Therapy at a Multisite Institution.

IntroductionFor many decades, the management of cancer has utilized radiation therapy, which continues to evolve with technology to improve patient outcomes. However, despite the standardization of treatment plans and the establishment of best clinical practices based on prospective, randomized trials and adherence to National Comprehensive Cancer Network (NCCN) guidelines, the outcomes from radiation therapy are highly variable and dependent on a number of factors, including patient demographics, tumor characteristics/histology, and treatment parameters. In this study, we attempt to use avail

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… .__)', 'Carcinoid tumor, malignant', 'Carcinoma in pleomorphic adenoma', 'Carcinoma, NOS', 'Carcinoma, anaplastic type, NOS', 'Carcinoma, metastatic, NOS', 'Carcinoma, undifferentiated type, NOS', 'Carcinoma-in-situ, NOS', 'Carcinosarcoma, NOS', 'Chondrosarcoma, NOS (T-170.__)', 'Chordoma', 'Chromophobe …

Prevalence and clinicopathological characteristics of de novo metastatic cancer at a major radiotherapy centre in West Africa: a cross-sectional study.

BackgroundCancer is a major public health challenge in West Africa, with a significant proportion of cancer-related deaths attributed to distant metastasis. De novo metastatic cancer (DnMC), where metastasis is detected at diagnosis, presents considerable therapeutic challenges, particularly in limited-resource settings where novel treatments are often unavailable and/or unaffordable.AimTo determine the prevalence, incidence and clinicopathological characteristics of patients diagnosed with DnMC at a major radiotherapy center in West Africa.MethodsThis was a single-institution-based quantitati

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… Carcinosarcomas of the uterine corpus accounted for 4.4% of the cases. Figure 8. Histological types of cancers with de novo metastasis. NST: no special type. Histological cancer types that were recorded in only a single patient were grouped together as ‘other’. …

A Systematic Pan-Cancer Analysis of YY1 Aberrations and their Relationship with Clinical Outcome, Tumor Microenvironment, and Therapeutic Targets.

Yin-Yang 1 (YY1) has a crucial function in the development of several malignancies, according to recent research. However, nothing is known about its aberrant expression and prognostic significance in human pan-cancer. We first explored the potential carcinogenic effect of YY1 in 33 cancers using the cancer genome atlas (TCGA) project and gene expression omnibus (GEO) datasets in this research. Then, we contained a variety of elements, for instance, gene expression, the state of survival, gene alterations, protein phosphorylation, immune infiltration, and related cellular pathways, and used a

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… 167 rectum adenocarcinoma (READ) tissues and 10 normal tissues, 263 sarcoma (SARC) tissues and 2 normal tissues, 471 SKCM tissues and 1 normal tissues, 375 STAD tissues and 32 normal tissues, 183 TGCT tissues, 119 THYM tissues and 2 normal tissues, 552 UCEC tissues and 35 normal tissues, 56 uterine carcinosarcoma …

Comprehensive analysis of TRIM56's prognostic value and immune infiltration in Pan-Cancer.

TRIM56 plays a role in tumor development through the ubiquitination of several key substrate molecules. However, its relationship with tumor prognosis and immune infiltration remains unclear. The expression and localization of TRIM56 were analyzed from TCGA_GTEx, TCGA and HPA database. The effects of TRIM56 on the proliferation and migration of lung cancer cells A549 were evaluated by CCK-8 and wound healing assays. Correlations between TRIM56 expression and survival in patients were analyzed using the Kaplan-Meier Plotter and a nomogram model. Additionally, the relationship between TRIM56 and

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… adrenocortical carcinoma), DLBC (diffuse large B-cell lymphoma), KICH (kidney chromophobe), LAML (acute myeloid leukemia), LGG (low-grade glioma), OV (ovarian serous cystadenocarcinoma), PAAD (pancreatic adenocarcinoma), SKCM (skin cutaneous melanoma), TGCT (testicular germ cell tumors), and UCS (uterine carcinosarcoma …

Presenting characteristics, histological subtypes and outcomes of adult central nervous system tumours: retrospective review of a surgical cohort.

IntroductionThe most recent local study on the incidence of histological subtypes of all brain and spinal tumours treated surgically was published in 2000. In view of the outdated data, we investigated the presenting characteristics, histological subtypes and outcomes of adult patients who underwent surgery for brain or spinal tumours at our institution.MethodsA single-centre retrospective review of 501 patients who underwent surgery for brain or spinal tumours from 2016 to 2020 was conducted. The inclusion criteria were (a) patients who had a brain or spinal tumour that was histologically ver

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… 0.2) Cervical squamous cell carcinoma | 1 (0.2) | 0 (0.0) | 1 (0.2) Bladder transitional cell carcinoma | 1 (0.2) | 0 (0.0) | 1 (0.2) Esophageal adenocarcinoma | 1 (0.2) | 0 (0.0) | 1 (0.2) Humeral osteosarcoma | 0 (0.0) | 1 (1.5) | 1 (0.2) Prostate carcinoma | 0 (0.0) | 1 (1.5) | 1 (0.2) Endometrial carcinosarcoma …

WT1: The Hinge Between Anemia Correction and Cancer Development in Chronic Kidney Disease.

Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) emerge as promising agents to treat anemia in chronic kidney disease (CKD) but the major concern is their correlated risk of cancer development and progression. The Wilms' tumor gene, WT1, is transcriptionally regulated by HIF and is known to play a crucial role in tumorigenesis and invasiveness of certain types of cancers. From the mechanism of action of HIF-PHIs, to cancer hypoxia and the biological significance of WT1, this review will discuss the link between HIF, WT1, anemia correction, and cancer. We aimed to reveal the re

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… Wilms' Tumor 1 Protein and Estrogen Receptor Beta Expression Are Associated with Poor Outcomes in Uterine Carcinosarcoma . Ann. Surg. Oncol. 20 ( 7 ), 2373 – 2379 . 10.1245/s10434-012-2838-9 23344579 Haase V. H. ( 2021 ). …

Immune infiltration related PRDX4 facilitates the malignant features and drug resistance of breast cancer.

The incidence of breast cancer continues to increase annually, posing a significant challenge for countries worldwide in terms of its prevention and treatment. Therefore, identifying novel therapeutic targets for breast cancer is urgently needed. The peroxiredoxin (PRDX) family is regarded as a good diagnostic marker for various tumors. However, the expression and prognostic significance of PRDX family members in breast cancer remain unclear and require systematic investigation. By using bioinformatic tools such as UALCAN, TIMER2.0, Human Protein Atlas Project (HPA), Gene Set Cancer Analysis (

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… pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma …

Trametinib in Patients With NF1-, GNAQ-, or GNA11-Mutant Tumors: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols S1 and S2.

PURPOSE: NCI-MATCH is a precision medicine trial using genomic testing to allocate patients with advanced malignancies to targeted treatment subprotocols. This report combines two subprotocols evaluating trametinib, a MEK1/2 inhibitor, in patients with Neurofibromatosis 1 (NF1[S1] or GNA11/Q [S2]) altered tumors. METHODS: Eligible patients had tumors with deleterious inactivating NF1 or GNA11/Q mutations by the customized Oncomine AmpliSeq panel. Prior MEK inhibitor treatment was excluded. Glioblastomas (GBMs) were permitted, including malignancies associated with germline NF1 mutations (S1 o

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… In addition, four patients experienced prolonged stable disease (SD), one each with GBM (PFS, 8.2 months), squamous cell carcinoma of the pharynx (7.3 months), neurofibroma (40.2 months), and carcinosarcoma of the fallopian tube (6.6 months). …

Selinexor in combination with topotecan in patients with advanced or metastatic solid tumors: Results of an open-label, single-center, multi-arm phase Ib study.

Background Selinexor, a first-in-class, oral selective inhibitor of nuclear export (SINE) compound inhibits Exportin-1(XPO1), had demonstrated synergistic activity with many chemotherapies and conferred in vivo antitumor efficacy in hematologic as well as solid tumors. Methods This open-label, single-center, multi-arm phase 1b study used a standard 3 + 3 design and a "basket type" expansion. Selinexor with intravenous topotecan was given in one of the 13 parallel arms. Patients with advanced or metastatic relapsed/refractory solid tumors following prior systemic therapy, or in whom the additio

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… Another patient with uterine carcinosarcoma who had 7 prior lines of therapies had SD with a TTF of 8 weeks. Four of the 5 patients with ovarian cancer were evaluable for efficacy. Two patients who progressed on 3 and 5 prior lines of therapies achieved SD with TTF of 9 and 17 weeks, respectively. …

Apigenin Inhibits IL-6 Transcription and Suppresses Esophageal Carcinogenesis.

Esophagus cancer is the seventh cause of cancer-related deaths globally. In this study, we analyzed interleukin 6 (IL-6) gene expression in human esophagus cancer patients and showed that IL-6 mRNA levels are significantly higher in tumor tissues and negatively correlated with overall survival, suggesting that IL-6 is a potential therapeutic target for esophagus cancer. We further demonstrated that apigenin, a nature flavone product of green plants, inhibited IL-6 transcription and gene expression in human esophagus cancer Eca-109 and Kyse-30 cells. Apigenin significantly and dose-dependently

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… Esophageal carcinosarcoma that was diagnosed as a granulocyte-colony stimulating factor and interleukin-6–producing tumor with a tumor fever. Intern. Med. 57, 2819–2825. 10.2169/internalmedicine.0677-17 Shukla S., Bhaskaran N., Babcook M. A., Fu P., Maclennan G. T., Gupta S. (2014). …

Mapping oncogenic protein interactions for precision medicine.

Normal protein-protein interactions (normPPIs) occur with high fidelity to regulate almost every physiological process. In cancer, this highly organised and precisely regulated network is disrupted, hijacked or reprogrammed resulting in oncogenic protein-protein interactions (oncoPPIs). OncoPPIs, which can result from genomic alterations, are a hallmark of many types of cancers. Recent technological advances in the field of mass spectrometry (MS)-based interactomics, structural biology and drug discovery have prompted scientists to identify and characterise oncoPPIs. Disruption of oncoPPI inte

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… Chemotherapy and/or radiotherapy in combination with surgery for ovarian carcinosarcoma. Cochrane Database Syst Rev. 2013;(2):CD006246. 2. Butts C, Socinski MA, Mitchell PL, et al. …

Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature.

Commonly used chemotherapeutic agents in oncology/hematology practice, causing toxic peripheral neuropathy, include taxanes, platinum compounds, vinca alkaloids, proteasome inhibitors, and antiangiogenic/immunomodulatory agents. This review paper intends to put together and discuss the spectrum of chemotherapy-induced peripheral neuropathy (CIPN) characteristics so as to highlight areas of future research to pursue on the topic. Current knowledge shows that the pathogenesis of CIPN still remains elusive, mostly because there are several sites of involvement in the peripheral nervous system. In

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… A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: a Gynecologic Oncology Group Study. Gynecol Oncol. 2000;79(2):147–153. doi: 10.1006/gyno.2000.6001. 69. Gatzemeier U, von Pawel J, Gottfried M, et al. …

Pathology Competencies in Medical Education and Educational Cases: Update 2023.

Pathology is a core component of medical school curricula because understanding the pathogenesis of the disease is foundational both for diagnostic efficiency and optimal use of ancillary resources in patient care. The Pathology Competencies for Medical Education (PCME) were developed as a national resource of expectations of pathology knowledge for medical students. The PCME are composed of three competencies: disease mechanisms and processes, organ system pathology, and diagnostic pathology and therapeutic pathology. The learning goals and learning objectives of the PCME that were first publ

Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma.

Retinoblastoma is the most common intraocular malignancy during childhood. Currently, there is no effective treatment for metastatic retinoblastoma. We investigated potential biomarkers of retinoblastoma by utilizing three datasets from a public database. Functional enrichment analysis, including gene ontology, Kyoto encyclopedia of genes and genomes, gene set enrichment analysis and variation analysis, suggested that differentially expressed genes in retinoblastoma were enriched in accelerated cell cycle events. Protein-protein interaction analysis constructed a network consisting of six hub

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… pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma …