Molecular subgroups of T-cell acute lymphoblastic leukemia in adults treated according to pediatric-based GMALL protocols.

In contrast to B-cell precursor acute lymphoblastic leukemia (ALL), molecular subgroups are less well defined in T-lineage ALL. Comprehensive studies on molecular T-ALL subgroups have been predominantly performed in pediatric ALL patients. Currently, molecular characteristics are rarely considered for risk stratification.

Case report: Sustained complete remission with all-oral MEPED therapy in a patient with Hodgkin's disease developing resistance to pembrolizumab.

Targeted chemotherapy and immune checkpoint inhibitors (ICPi) have expanded the spectrum of therapies for patients with relapsed/refractory (r/r) Hodgkin's disease and significantly improved the proportion of patients with long-term disease control. However, there is no standardized therapeutic option in case of further progression. Recently, we demonstrated that therapy with MEPED (metronomic chemotherapy, everolimus, pioglitazone, etoricoxib, dexamethasone) is highly effective in patients with r/r Hodgkin's disease.

Addressing Genetic Tumor Heterogeneity, Post-Therapy Metastatic Spread, Cancer Repopulation, and Development of Acquired Tumor Cell Resistance.

The concept of post-therapy metastatic spread, cancer repopulation and acquired tumor cell resistance (M-CRAC) rationalizes tumor progression because of tumor cell heterogeneity arising from post-therapy genetic damage and subsequent tissue repair mechanisms. Therapeutic strategies designed to specifically address M-CRAC involve tissue editing approaches, such as low-dose metronomic chemotherapy and the use of transcriptional modulators with or without targeted therapies. Notably, tumor tissue editing holds the potential to treat patients, who are refractory to or relapsing (r/r) after conventional chemotherapy, which is usually based on administering a maximum tolerable dose of a cytostatic drugs.

All-oral low-dose chemotherapy TEPIP is effective and well-tolerated in patients with peripheral T-cell lymphoma.

Purpose: Peripheral T-cell lymphoma (PTCL) is a rare and heterogenous hematologic malignancy with poor prognosis especially in elderly and frail patients who are not eligible for intensive treatment. The resulting palliative setting necessitates tolerable but effective schedules for outpatient treatment. TEPIP is a locally developed, all-oral low-dose regimen comprising trofosfamide, etoposide, procarbazine, idarubicin, and prednisolone.

Light-induced homolysis of copper(ii)-complexes - a perspective for photocatalysis.

Over the past decade, photocatalysis has developed into a powerful strategy for the selective functionalization of molecules through radical intermediates. Besides the well-established iridium- or ruthenium-based photocatalysts, which ideally fulfill the requirements for a photocatalyst, such as long excited-state lifetimes and photostability, the shift towards earth-abundant metal-based photocatalysts has so far been less explored. The concept of light-induced homolysis (LIH) for generating radicals has recently gained significant interest as a new platform for inducing photoreactions with earth-abundant 3d-metal complexes despite only having excited-state lifetimes in the low nanosecond range or even below.

Androgen Deprivation Freezes Hormone-Sensitive Prostate Cancer Cells in a Reversible, Genetically Unstable Quasi-Apoptotic State, Bursting into Full Apoptosis upon Poly(ADP-ribose) Polymerase Inhibition.

Androgen deprivation therapy (ADT) is a powerful treatment for metastatic hormone-sensitive prostate cancer (mHSPC) patients, but eventually and inevitably, cancer relapses, progressing to the fatal castration-resistant (CR)PC stage. Progression implies the emergence of cells proliferating in the absence of androgen through still elusive mechanisms. We show here for the first time that ADT induces LNCaP mHSPC cells to collectively enter a metastable quasi-apoptotic state (QUAPS) consisting of partial mitochondrial permeabilization, limited BAX and caspase activation, and moderate induction of caspase-dependent dsDNA breaks; despite this, cells maintain full viability.

Copper(I) Photocatalyzed Bromonitroalkylation of Olefins: Evidence for Highly Efficient Inner-Sphere Pathways.

We report the visible light-mediated copper-catalyzed vicinal difunctionalization of olefins utilizing bromonitroalkanes as ATRA reagents. This protocol is characterized by high yields and fast reaction times under environmentally benign reaction conditions with exceptional scope, allowing the rapid functionalization of both activated and unactivated olefins. Moreover, late-stage functionnalization of biologically active molecules and upscaling to gram quantities is demonstrated, which offers manifold possibilities for further transformations, e.

Biomodulatory therapy induces durable remissions in multi-system Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is rare hematological neoplasia originating from the aberrant proliferation of CD207-positive dendritic cells. Refractory multi-system LCH is difficult to treat necessitating the continuous development of different salvage therapies. At our medical center, eleven patients (age 11 months to 77 years) with multi-system LCH were treated on a compassionate use basis with metronomic biomodulation therapy (MBT) involving the daily oral application of low-dose trofosfamide, etoricoxib, pioglitazone and low-dose dexamethasone.

Drug Repurposing by Tumor Tissue Editing.

The combinatory use of drugs for systemic cancer therapy commonly aims at the direct elimination of tumor cells through induction of apoptosis. An alternative approach becomes the focus of attention if biological changes in tumor tissues following combinatory administration of regulatorily active drugs are considered as a therapeutic aim, e.g.

Case Report: Extramedullary Acute Promyelocytic Leukemia: An Unusual Case and Mini-Review of the Literature.

Background: Acute promyelocytic leukemia (APL) constitutes a serious hematological emergency necessitating rapid diagnosis and therapy to prevent lethal bleedings resulting from APL-induced thrombocytopenia and coagulopathy. Atypical manifestations of APL, such as extramedullary disease at first presentation, pose diagnostic challenges and delay the onset of appropriate therapy. Nevertheless, extramedullary manifestations of APL are mostly accompanied by blood count alterations pointing to an underlying hematological disease.

All-Oral Low-Dose Chemotherapy TEPIP is Effective and Well-Tolerated in Relapsed/Refractory Patients With Aggressive B-Cell Lymphoma.

Purpose: Treatment options in patients (pts.) with advanced relapsed and refractory aggressive B-cell lymphoma are limited. Palliative all-oral chemotherapy regimens reduce in-patient visits and contribute to quality of life.

A Proteomic Platform Enables to Test for AML Normalization .

Acute promyelocytic leukaemia (APL) can be cured by the co-administration of arsenic trioxide (ATO) and all- retinoic acid (ATRA). These small molecules relieve the differentiation blockade of the transformed promyelocytes and trigger their maturation into functional neutrophils, which are physiologically primed for apoptosis. This normalization therapy represents a compelling alternative to cytotoxic anticancer chemotherapy, but lacks an model system for testing the efficiency of novel combination treatments consisting of inducers of differentiation and metallopharmaceuticals.

Apoptosis as Driver of Therapy-Induced Cancer Repopulation and Acquired Cell-Resistance (CRAC): A Simple In Vitro Model of Phoenix Rising in Prostate Cancer.

Apoptotic cells stimulate compensatory proliferation through the caspase-3-cPLA-2-COX-2-PGE-2-STAT3 Phoenix Rising pathway as a healing process in normal tissues. Phoenix Rising is however usurped in cancer, potentially nullifying pro-apoptotic therapies. Cytotoxic therapies also promote cancer cell plasticity through epigenetic reprogramming, leading to epithelial-to-mesenchymal-transition (EMT), chemo-resistance and tumor progression.

The Translational Role of MUC8 in Salivary Glands: A Potential Biomarker for Salivary Stone Disease?

Mucin (MUC) 8 has been shown to play an important role in respiratory disease and inflammatory responses. In the present study, we investigated the question of whether MUC8 is also produced and secreted by salivary glands and whether it may also play a role in the oral cavity in the context of inflammatory processes or in the context of salivary stone formation. Tissue samples from parotid and submandibular glands of body donors ( = 6, age range 63-88 years), as well as surgically removed salivary stones from patients ( = 38, age range 48-72 years) with parotid and submandibular stone disease were immunohistochemically analyzed targeting MUC8 and TNFα.

Biomodulatory Treatment Regimen, MEPED, Rescues Relapsed and Refractory Classic Hodgkin's Disease.

Current combined intensive chemotherapy and radiation regimens yield excellent survival rates in advanced classic Hodgkin's lymphoma (cHL). However, acute toxicity in elderly, comorbid patients can be challenging and long-term survival in refractory patients remains poor. We report on six patients with r/r HL, three patients with long-term follow-up, three newly treated, after biomodulatory therapy.

Continuous Complete Remission in Two Patients with Acute Lymphoblastic Leukemia and Severe Fungal Infection Following Short-Term, Dose-Reduced Chemotherapy.

Spontaneous remission in acute lymphoblastic leukemia (ALL) is a rare phenomenon, which typically involves a pattern of feverish or septic disease followed by quick but mostly transient remission. We report on two male patients (46-year-old (pt. 1) and 19-year-old (pt.

Characteristics and outcome of patients with low-/intermediate-risk acute promyelocytic leukemia treated with arsenic trioxide: an international collaborative study.

The aim of this study was to characterize a large series of 154 patients with acute promyelocytic leukemia (median age, 53 years; range, 18-90 years) and evaluate real-life outcome after up-front treatment with arsenic trioxide and all-trans retinoic acid. All patients were included in the prospective NAPOLEON registry (NCT02192619) between 2013 and 2019. The acute promyelocytic leukemia was de novo in 91% (n=140) and therapy-related in 9% (n=14); 13% (n=20) of the patients were older than 70 years.

A Randomized Phase II Trial Comparing the Efficacy and Safety of Pioglitazone, Clarithromycin and Metronomic Low-Dose Chemotherapy with Single-Agent Nivolumab Therapy in Patients with Advanced Non-small Cell Lung Cancer Treated in Second or Further Line (ModuLung).

Most non-small cell lung cancers occur in elderly and frequently comorbid patients. Therefore, it is necessary to evaluate the efficacy of biomodulatory active therapy regimen, concertedly interfering with tumor-associated homeostatic pathways to achieve tumor control paralleled by modest toxicity profiles. The ModuLung trial is a national, multicentre, prospective, open-label, randomized phase II trial in patients with histologically confirmed stage IIIB/IV squamous ( = 11) and non-squamous non-small cell ( = 26) lung cancer who failed first-line platinum-based chemotherapy.