Breast cancer is a heterogeneous disease and a leading malignancy around the world. It is a vital cause of untimely mortality among women. Drug resistance is the major challenge for effective cancer therapeutics. In contrast, cancer stem cells (CSCs) are one of the reasons for drug resistance, tumor progression, and metastasis. The small population of CSCs present in each tumor has the ability of self-renewal, differentiation, and tumorigenicity. CSCs are often identified and enriched using a variety of cell surface markers (CD44, CD24, CD133, ABCG2, CD49f, LGR5, SSEA-3, CD70) that exert their functions by different regulatory networks, i.e., Notch, Wnt/β-catenin, hedgehog (Hh), and Hippo signaling pathways. Particularly the Hippo signaling pathway is the emerging and very less explored cancer stem cell pathway. Here, in this review, the Hippo signaling molecules are elaborated with respect to their ability of stemness as epigenetic modulators and how these molecules can be targeted for better cancer treatment and to overcome drug resistance.

Prostate cancer (PC) is identified as a heterogeneous disease. About 20 to 30% of PC patients experience cancer recurrence, characterized by an increase in the antigen termed serum prostate-specific antigen (PSA). Clinical recurrence of PC commonly occurs after five years. Metastatic castration-resistant prostate cancer (mCRPC) has an intricate genomic background. Therapies that target genomic changes in DNA repair signaling pathways have been progressively approved in the clinic. Innovative therapies like targeting signaling pathways, bone niche, immune checkpoint, and epigenetic marks have been gaining promising results for better management of PC cases with bone metastasis. This review article summarizes the recent consideration of the molecular mechanisms and signaling pathways involved in local and metastatic prostate cancer, highlighting the clinical insinuations of the novel understanding.

Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease sharing some phenotypic, genetic, and immunological features with both type 1 and 2 diabetes. Patients with LADA have a relatively slow autoimmune process and more residual islet β-cell function at onset, allowing a time window to protect residual islet β cells and delay or inhibit disease progression. It is crucial to discover various heterogeneous factors affecting islet β-cell function for precise LADA therapy. In this review, we first describe the natural history of LADA. Thereafter, we summarize β-cell function-related heterogeneous factors in LADA, including the age of onset, body mass index, genetic background, and immune, lifestyle, and environmental factors. In parallel, we evaluate the impact of current hypoglycemic agents and immune intervention therapies for islet β-cell protection. Finally, we discuss the opportunities and challenges of LADA treatment from the perspective of islet β-cell function protection.

Breast cancer is one of the most prevalent malignant diseases, and one of the main causes of mortality among women across the world. Despite advances in chemotherapy, drug resistance remains a major clinical concern, creating an urgent need to explore novel anti-breast cancer drugs. 1,2,3-triazole is a privileged moiety, and its derivatives could inhibit cancer cell proliferation and induce cell cycle arrest and apoptosis. Accordingly, 1,2,3-triazole derivatives possess profound activity against various cancers, including breast cancer. This review summarizes the latest progress related to the anti-breast cancer potential of 1,2,3-triazole derivatives, covering articles published from January 2017 to December 2021. The mechanisms of action and structure-activity relationships (SARs) are also discussed for the further rational design of more effective candidates.

Medulloblastoma is a highly aggressive \"small round blue cell tumor\" of the posterior fossa predominantly seen in children. Historically aggressive multimodality regimens have achieved encouraging outcomes with the caveat of severe long-term toxicities. The last decade has unleashed a revolution in terms of evolved understanding of this heterogeneous disease entity in terms of molecular biology. Medulloblastoma as of today is grouped into one of four canonical molecular subgroups (WNT, SHH, Group 3, and Group 4) each characterized by different putative cells of origin, characteristic aberrations at the molecular level, radiogenomics, and outcomes. Our understanding continues to grow in this regard. The future promises much in terms of personalized medicine in tailoring therapy to the needs of individual patients based on their clinical and molecular profile in order to maximize individual and population based outcomes at the cost of minimizing toxicity.

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Genetic studies provide valuable information to assess if the effect of genetic variants varies by the nongenetic \"environmental\" variables, what is traditionally defined to be gene-environment interaction (GxE). A common complication is that multiple disease states present with the same set of symptoms, and hence share the clinical diagnosis. Because (a) disease states might have distinct genetic bases; and (b) frequencies of the disease states within the clinical diagnosis vary by the environmental variables, analyses of association with the clinical diagnosis as an outcome variable might result in false positive or false negative findings. We develop estimates for this setting to be able to assess GxE in a case-only study and we compare the case-control and case-only estimates. We report extensive simulation studies that evaluate empirical properties of the estimates and show the application to a study of Alzheimer\'s disease.

Unmet clinical diagnostic needs exist for many complex diseases, which (it is hoped) will be solved by the discovery of metabolomics biomarkers. However, at present, no diagnostic tests based on metabolomics have yet been introduced to the clinic. This review is presented as a research perspective on how data analysis methods in metabolomics biomarker discovery may contribute to the failure of biomarker studies and suggests how such failures might be mitigated. The study design and data pretreatment steps are reviewed briefly in this context, and the actual data analysis step is examined more closely.

OBJECTIVE: There are 2 types of amyloidosis caused by transthyretin deposits: the wild type (wt-ATTR) and the mutant type (m-ATTR), transmitted by autosomal dominant inheritance with variable penetrance, manifesting with neurological and/or cardiac symptoms. We report on 3 families affected by m-ATTR diagnosed in a nonendemic area.
METHODS: We studied 63 patients with a high suspicion of ATTR. The diagnosis was subsequently performed by magnification through polymerase chain reaction of DNA. For the positive cases, we studied the first-degree relatives.
RESULTS: We detected 7 positive cases of m-ATTR, distributed among 3 families (Glu74Gln, Val142Ile in heterozygosity and Val142Ile in homozygosity), and 3 cases of nonpathogenic variants.
CONCLUSIONS: Hereditary ATTR is a rare disease but is present in nonendemic areas and should therefore be considered in the differential diagnosis of patients with polyneuropathy and/or heart failure with preserved ejection fraction.

A 15-year-old male patient was admitted to hospital having experienced repeated fractures over the previous three years, predominantly due to falling down or overexertion. The clinical signs and radiological features, such as recurrent fractures, blue sclera and low bone mineral density (BMD) level, all led to the diagnosis of a mild form of osteogenesis imperfecta (OI) type I. The patient began treatment with a regular intake of calcium (1,000 mg/day), an adequate intake of vitamin D (800 U/day) and intravenous pamidronate (60 mg). Following four months of treatment, the symptoms and quality of life of the patient improved. This patient appears to be a rare case of OI type I.