79 results match your criteria: "Mannheim Cancer Center[Affiliation]"

Recent advancements in cancer treatment have shown the potential of immune checkpoint blockade (ICB) plus L. therapy in improving survival rates for patients with advanced or metastatic non-small-cell lung cancer (NSCLC). The objective of this study was to investigate factors associated with improved survival in NSCLC patients treated with a combination of ICB and abnobaViscum.

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E3 ubiquitin ligase RNF10 promotes dissociation of stalled ribosomes and responds to ribosomal subunit imbalance.

Nat Commun

November 2024

Division of Biochemistry, Mannheim Institute for Innate Immunoscience (MI3) and Mannheim Cancer Center (MCC), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.

Article Synopsis
  • - Aberrant translation causes ribosome stalling, leading to ribosomal protein ubiquitination and activation of quality control, with RNF10 playing a key role in this process by monoubiquitinating RPS3.
  • - RNF10 helps dissociate 40S ribosomal subunits from stalled ribosomes during both translation elongation and initiation, preventing the formation of ribosomal half-mers.
  • - The levels of RNF10 are tightly linked to the availability of 40S subunits, as knockdowns of RPS or RPL proteins can either lead to RNF10 degradation or accumulation, respectively, indicating that RNF10 is crucial for dealing with imbalances in ribosomal subunit production.
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Purpose: Contrary to guidelines, many cancer patients are not screened for cancer-related fatigue (CRF) and do not receive information or adequate treatment. As physicians play a key role in cancer therapy, their knowledge of this common sequela and perspectives on its management are of major interest.

Methods: For an online survey, physicians working in oncology in Germany were systematically drawn from registers and invited by using institutional newsletters or colleagues.

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Background: Radiation science is of utmost significance not only due to its growing importance for clinical use, but also in everyday life such as in radiation protection questions. The expected increase in cancer incidence due to an aging population combined with technical advancements further implicates this importance and results in a higher need for sufficient highly educated and motivated personnel. Thus, factors preventing young scientists and medical personnel from entering or remaining in the field need to be identified.

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Examining nirogacestat for adults with progressing desmoid tumors who require systemic treatment.

Expert Opin Pharmacother

November 2024

Sarcoma Unit, Mannheim Cancer Center (MCC), Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany.

Article Synopsis
  • - Desmoid tumor (DT) is a rare and aggressive type of tumor that can develop anywhere in the body, and medical therapies are crucial for patients needing treatment.
  • - Nirogacestat, a newly approved γ-secretase inhibitor, is the first FDA-approved drug specifically for treating DTs and works by targeting the NOTCH signaling pathway.
  • - Despite the introduction of Nirogacestat, there is still a lack of high-quality evidence for systemic treatments for DTs, and physicians must consider various factors when choosing a treatment plan, as well as monitor long-term safety and efficacy.
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Carnosine is an endogenous dipeptide characterized by a multimodal mechanism of action. However, its clinical potential is limited by serum and cytosolic carnosinases, which significantly reduce its bioavailability. Based on that, different research groups have worked on the development of new strategies able not only to prevent its rapid metabolization but also to improve its distribution and specific targeting.

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Optimising inter-patient image registration for image-based data mining in breast radiotherapy.

Phys Imaging Radiat Oncol

October 2024

Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Christie NHS Foundation Trust Hospital, Manchester, United Kingdom.

Article Synopsis
  • IBDM for breast radiotherapy needs better spatial normalisation due to differences in treatment positioning and breast characteristics, prompting an optimization study.
  • Data from 996 patients were analyzed using various deformable image registration methods to improve the accuracy of spatial normalisation during treatment.
  • The B-spline algorithm with normalised mutual information was identified as the most effective method, with supine registrations achieving the highest accuracy, while arm positioning did not significantly affect outcomes.
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Guidelines of Onkopedia: What Is New? Locally Advanced Rectal Cancer.

Oncol Res Treat

December 2024

Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie (DGHO) Berlin, Berlin, Germany.

This article briefly summarizes clinically relevant new aspects of the recently published German, Austrian, and Swiss Onkopedia guideline for the treatment of locally advanced rectal cancer. Main aspects comprise (i) the use of total neoadjuvant therapy for rectal cancers with high-risk features, (ii) treatment with neoadjuvant chemotherapy for patients with a low risk for local recurrence, (iii) immunotherapy using dostarlimab in patients with MSI high/dMMR rectal cancer, as well as (iv) the implementation of organ sparing treatment concepts. The availability of several evidence-based treatment options requires intensive discussion within the multidisciplinary team as well as dedicated information for patients about treatment goals, options, and risks of individual treatment approaches.

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Background: Neoadjuvant chemotherapy is an option for patients with locally advanced rectal cancer at low risk for local recurrence. This randomized phase II trial investigated whether the addition of aflibercept to modified FOLFOX6 (mFOLFOX6) could improve the rates of centrally confirmed pathological complete remissions (pCR) and (disease-free) survival in magnetic resonance imaging (MRI)-staged cT3 rectal cancer.

Patients And Methods: Patients with rectal cancer fulfilling the following criteria were included: lower border of tumor >5 cm and <16 cm from anal verge; circumferential resection margin >2 mm and T3-tumor with a maximum infiltration of 10 mm, as determined by MRI.

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Functional status and quality of life in older patients with advanced esophageal squamous cell cancer receiving second-line nivolumab ± ipilimumab therapy: A post hoc analysis of the phase 2, multicenter RAMONA study.

J Geriatr Oncol

September 2024

Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address:

Introduction: The phase 2 RAMONA study demonstrated that second-line nivolumab ± ipilimumab immunotherapy was feasible and effective in older patients with advanced esophageal squamous cell cancer (ESCC). Here, we presented results from functional status (FS) and quality-of-life (QoL) analyses.

Materials And Methods: Patients aged ≥65 years with advanced ESCC and disease progression following first-line therapy were enrolled for study treatment with nivolumab ± ipilimumab.

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Introduction: Ewing sarcoma (ES), is a rare cancer affecting children, adolescents and adults. After VIDE (vincristine-ifosfamide-doxorobucin-etoposide) induction chemotherapy, Busulfan-Melphalan (BuMel) high-dose chemotherapy followed by autologous hematopoietic stem cells transplantation improved outcomes in unfavourable localized ES, but with more toxicities than conventional chemotherapy (VAI: Vincristine-dactinomycin-Ifosfamide). We evaluated whether the risk of acute toxicity associated with BuMel compared to VAI varied according to age in patients recruited in the R2Loc and R2Pulm randomised trials of the Euro-E.

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Lost in translation: How neurons cope with tRNA decoding.

Bioessays

September 2024

Division of Biochemistry, Mannheim Institute for Innate Immunoscience (MI3), Mannheim Cancer Center (MCC), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Post-transcriptional tRNA modifications contribute to the decoding efficiency of tRNAs by supporting codon recognition and tRNA stability. Recent work shows that the molecular and cellular functions of tRNA modifications and tRNA-modifying-enzymes are linked to brain development and neurological disorders. Lack of these modifications affects codon recognition and decoding rate, promoting protein aggregation and translational stress response pathways with toxic consequences to the cell.

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Introduction: While available systemic treatments have modest long term efficacy in advanced angiosarcoma, immunotherapy represents an interesting new therapeutic opportunity. To establish its benefit, it is required to conduct a clinical trial assessing its efficacy and toxicity compared to standard treatments.

Material And Methods: This is a literature review from PubMed search.

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Current Management of Desmoid Tumors: A Review.

JAMA Oncol

August 2024

Department of Surgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy.

Article Synopsis
  • Desmoid tumors (DT) are rare, aggressive growths that have historically been treated primarily with surgery, but recent trends suggest a shift towards less invasive treatment options.
  • A consensus meeting held in Milan in June 2023 aimed to update global guidelines for DT management, bringing together over 90 experts and patient advocates to discuss new strategies and treatments.
  • The updated guidelines emphasize the importance of local therapies and include information on the latest medical agents, particularly γ-secretase inhibitors, to ensure informed and effective management of DT in specialized referral centers.
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Article Synopsis
  • This study investigates using intraoperative radiotherapy (IORT) as an additional boost for high-risk breast cancer patients, combined with standard external beam radiotherapy (EBRT), and aims to evaluate treatment outcomes and side effects.
  • The study, known as TARGIT BQR, included 1133 patients across 10 centers from 2011 to 2020, assessing both acute and long-term toxicity following the IORT boost delivered immediately after tumor removal.
  • Findings showed that the IORT boost is feasible and generally safe, with low rates of serious side effects; however, some patients experienced mild to moderate acute and chronic effects such as erythema and fibrosis.
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Article Synopsis
  • - Desmoid tumors (DT) are rare, locally aggressive sarcomas that often affect younger females (under 40), primarily causing high symptom burden and significant reductions in quality of life, despite having a good overall survival rate.
  • - Common symptoms include pain, fatigue, and insomnia, with some patients experiencing disfigurement or mobility issues; anxiety and depression rates in DT patients can mirror those in more severe cancers.
  • - The GOunder/Desmoid Tumor Research Foundation's DEsmoid Symptom/Impact Scale (GODDESS) evaluates patient-reported outcomes specific to DT, aiding in clinical trials to incorporate patient perspectives as new treatments are developed.
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Active surveillance and emerging medical treatment options for desmoid: when and for whom?

Curr Opin Oncol

July 2024

Department of Medical Oncology, University of Heidelberg, Mannheim University Medical Center, Mannheim Cancer Center (MCC), Sarcoma Unit, Mannheim, Germany.

Article Synopsis
  • This article reviews updated strategies for managing desmoid tumors, highlighting recent research and approaches.
  • Active surveillance has emerged as the main management technique, showing about 50% of cases stabilize or regress without immediate intervention, supported by recent studies with notable progression-free survival rates.
  • Additional randomized trials have investigated medical treatments for more aggressive cases, showing that drugs like sorafenib, pazopanib, and nirogacestat have potential benefits in improving patient outcomes.
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Immunotherapy with PD-1/PD-L1 inhibitors has significantly improved the survival rates of patients with metastatic non-small-cell lung cancer (NSCLC). Results of a real-world data study investigating add-on VA ( L.) to chemotherapy have shown an association with the improved overall survival of patients with NSCLC.

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Background: Panel gene sequencing is an established diagnostic tool for precision oncology of solid tumors, but its utility for the treatment of cancers of the digestive system in clinical routine is less well documented.

Methods: We retrospectively identified patients with advanced or metastatic gastrointestinal, pancreaticobiliary or hepatic cancers who received panel gene sequencing at a tertiary university hospital from 2015 to 2022. For these cases, we determined the spectrum of genetic alterations, clinicopathological parameters and treatment courses.

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HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments.

Cancers (Basel)

March 2024

Klinik und Poliklinik für Innere Medizin III, Klinikum rechts der Isar der TU München, 81675 Munich, Germany.

Despite a decreasing incidence in Western countries, gastric cancer is among the most common cancer subtypes globally and is associated with one of the highest tumor-related mortality rates. Biomarkers play an increasing role in the treatment against gastric cancer. HER2 was one of the first biomarkers that found its way into clinical practice.

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Turnover of PPP1R15A mRNA encoding GADD34 controls responsiveness and adaptation to cellular stress.

Cell Rep

April 2024

Heidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research, 69120 Heidelberg, Germany. Electronic address:

The integrated stress response (ISR) is a key cellular signaling pathway activated by environmental alterations that represses protein synthesis to restore homeostasis. To prevent sustained damage, the ISR is counteracted by the upregulation of growth arrest and DNA damage-inducible 34 (GADD34), a stress-induced regulatory subunit of protein phosphatase 1 that mediates translation reactivation and stress recovery. Here, we uncover a novel ISR regulatory mechanism that post-transcriptionally controls the stability of PPP1R15A mRNA encoding GADD34.

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Developing new drugs or generating evidence for existing drugs in new indications for ultra-rare cancers is complex and carries a high-risk of failure. This gets even harder in ultra-rare tumours, which have an annual incidence of 1 per 1,000,000 population or less. Here, we illustrate the problem of adequate evidence generation in ultra-rare tumours, using Alveolar Soft-Part Sarcomas (ASPS) - an ultra-rare sarcoma newly diagnosed in approximately 60 persons a year in the European Union - as an exemplar case showing challenges in development despite being potentially relevant for classes of agents.

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[Locally Advanced Rectal Cancer: New Neoadjuvant Strategies and Total Neoadjuvant Therapy].

Zentralbl Chir

February 2024

Mannheim Cancer Center, Universität Heidelberg, Universitätsmedizin Mannheim, Mannheim, Deutschland.

Treatment strategies for locally advanced rectal cancer are changing significantly. The treatment recommended in German guidelines for locally advanced tumors of neoadjuvant radio(chemo)therapy (RChT), followed by surgery and, if necessary, adjuvant therapy, are increasingly be abandoned in favor of the following concepts: (i) prolonged neoadjuvant therapy (i.e.

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