Intensive post-remission therapy does not decrease relapse after allotransplants for acute myeloid leukaemia in 1st remission and should not be given
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Predictors of relapse after discontinuing antipsychotics in patients with schizophrenia spectrum disorders
We studied 61 patients with schizophrenia spectrum disorders who discontinued medication after achieving symptomatic remission. Over 3 years, relapse rates were significantly higher in those not meeting full recovery (p = 0.006) or remission (p < 0.001) criteria, with rates up to twice as high. Significant differences between relapsed and maintained groups included age at onset (p = 0.004), age at discontinuation (p = 0.009), and proportions meeting full recovery (p = 0.001) or remission (p = 0.003). Univariate Cox regression identified older age of onset (p = 0.038), lack of full recovery (p = 0.008) or remission (p = 0.001), and higher positive symptom score (p = 0.018) as predictors of relapse. In multivariate analysis, only full remission remained significant (p = 0.002). Our findings suggest that in making decision about discontinuation, applying more strict approaches, i.e., full recovery or remission criteria and detailed assessment of positive symptoms are critical and essential.
Challenges determining the best target duration of deep molecular response after which to attempt achieving therapy-free remission in chronic myeloid leukaemia
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MiRNAs as biomarkers of nutritional therapy to achieve T2DM remission in patients with coronary heart disease: from the CORDIOPREV study
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A mathematical framework for comparison of intermittent versus continuous adaptive chemotherapy dosing in cancer
Chemotherapy resistance in cancer remains a barrier to curative therapy in advanced disease. Dosing of chemotherapy is often chosen based on the maximum tolerated dosing principle; drugs that are more toxic to normal tissue are typically given in on-off cycles, whereas those with little toxicity are dosed daily. When intratumoral cell-cell competition between sensitive and resistant cells drives chemotherapy resistance development, it has been proposed that adaptive chemotherapy dosing regimens, whereby a drug is given intermittently at a fixed-dose or continuously at a variable dose based on tumor size, may lengthen progression-free survival over traditional dosing. Indeed, in mathematical models using modified Lotka-Volterra systems to study dose timing, rapid competitive release of the resistant population and tumor outgrowth is apparent when cytotoxic chemotherapy is maximally dosed. This effect is ameliorated with continuous (dose modulation) or intermittent (dose skipping) adaptive therapy in mathematical models and experimentally, however, direct comparison between these two modalities has been limited. Here, we develop a mathematical framework to formally analyze intermittent adaptive therapy in the context of bang-bang control theory. We prove that continuous adaptive therapy is superior to intermittent adaptive therapy in its robustness to uncertainty in initial conditions, time to disease progression, and cumulative toxicity. We additionally show that under certain conditions, resistant population extinction is possible under adaptive therapy or fixed-dose continuous therapy. Here, continuous fixed-dose therapy is more robust to uncertainty in initial conditions than adaptive therapy, suggesting an advantage of traditional dosing paradigms.
Targeting of TAMs: can we be more clever than cancer cells?
With increasing incidence and geography, cancer is one of the leading causes of death, reduced quality of life and disability worldwide. Principal progress in the development of new anticancer therapies, in improving the efficiency of immunotherapeutic tools, and in the personification of conventional therapies needs to consider cancer-specific and patient-specific programming of innate immunity. Intratumoral TAMs and their precursors, resident macrophages and monocytes, are principal regulators of tumor progression and therapy resistance. Our review summarizes the accumulated evidence for the subpopulations of TAMs and their increasing number of biomarkers, indicating their predictive value for the clinical parameters of carcinogenesis and therapy resistance, with a focus on solid cancers of non-infectious etiology. We present the state-of-the-art knowledge about the tumor-supporting functions of TAMs at all stages of tumor progression and highlight biomarkers, recently identified by single-cell and spatial analytical methods, that discriminate between tumor-promoting and tumor-inhibiting TAMs, where both subtypes express a combination of prototype M1 and M2 genes. Our review focuses on novel mechanisms involved in the crosstalk among epigenetic, signaling, transcriptional and metabolic pathways in TAMs. Particular attention has been given to the recently identified link between cancer cell metabolism and the epigenetic programming of TAMs by histone lactylation, which can be responsible for the unlimited protumoral programming of TAMs. Finally, we explain how TAMs interfere with currently used anticancer therapeutics and summarize the most advanced data from clinical trials, which we divide into four categories: inhibition of TAM survival and differentiation, inhibition of monocyte/TAM recruitment into tumors, functional reprogramming of TAMs, and genetic enhancement of macrophages.
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