Efficacy of Infliximab for the Treatment of Oral Manifestation of Crohn's Disease.

Oral manifestations of IBD can be specific or nonspecific, due to intestinal malabsorption or induced by pharmacological treatments. Oral manifestations may precede the diagnosis of IBD or interfere with timely diagnosis and treatment. The paradigm of treatment for oral lesions in patients with IBD is based on treating and controlling the intestinal manifestations of the underlying disease as well as local methods of treatment can be used. Here, we report a case of a patient with the oral manifestation of IBD, who responded to treatment with infliximab. The patient was admitted with complaints of long-term nonhealing ulcers of the lips and oral cavity, odynophagia, and there were no intestinal manifestations at that time. The appearance of the disease in 2008 with lesions of the oral cavity, however, Crohn's disease was diagnosed in 2016. The patient began therapy with azathioprine and prednisolone, and later developed hormone dependence and osteoporosis. In 2020, against the background of immunosuppressive therapy, the patient has an exacerbation, especially increased symptoms from the lesion of the oral cavity. In 2020 was started therapy with vedolizumab, with slight improvement. Due to the ineffectiveness of the latter's therapy, therapy with monoclonal antibodies (infliximab) was started in February 2021. Currently, patient is in clinical, laboratory, and endoscopic remission.

The Oxidative Drug Combination for Suppressing KRAS G12D Inducible Tumour Growth.

Background: Kirsten rat sarcoma (KRAS) protein is an essential contributor to the development of pancreatic ductal adenocarcinoma (PDAC). KRAS G12D and G12V mutant tumours are significant challenges in cancer therapy due to high resistance to the treatment. Objective: To determine how effective is the ATO/D-VC combination in suppression of PDAC the mouse transgenic model. This study investigated the antitumour effect of a novel combination of arsenic trioxide (ATO) and D-ascorbic acid isomer (D-VC). Such a combination can be used to treat KRAS mutant cancer by inducing catastrophic oxidative stress. Methods: In this study, we examined the effectiveness of ATO and D-VC on xenograft models-AK192 cells transplanted into mice. Previously, it has been shown that a high concentration of Vitamin C (VC) selectively can kill the cells expressing KRAS. Results: The results of this study demonstrated that the combination of VC with a low dose of the oxidizing drug ATO led to the enhancement of the therapeutic effect. These findings suggest that the combined treatment using ATO and D-VC is a promising approach to overcome the limitation of drug selectivity and efficacy.

Trends of Colorectal Cancer Prevalence in Kazakhstan Related to Screening.

We carried out an analysis of the total incidence of colon cancer throughout Kazakhstan. Retrospectively, according to the regional reports on endoscopic screening, the study showed an increase in the age-related incidence of colorectal cancer (CRC) cases from 2004-2008 to 2009-2014. The peak of morbidity in both periods was noted in the age category of >70 years. The indicators of the territorial distribution of CRC incidence make it possible to divide the regions into areas with low or high rates of CRC. Specific indicators showed newly diagnosed cases of CRC stages I, II, III, and IV in 2004-2018. The incidence rates of stages I and II showed a two-fold increase (35%-67.4%) and the incidence of stage IV showed a decline from 19.3% to 13.1% and of stage III from 45.7% to 19.5% from 2004 to 2018, respectively. An analysis of CRC incidence throughout Kazakhstan showed an increase in the overall incidence. Since population-based CRC screening was introduced in 2011, the morbidity was found to increase for stages I and II.

Novel Small Molecule Inhibitors of Cancer Stem Cell Signaling Pathways.

The main aim of oncologists worldwide is to understand and then intervene in the primary tumor initiation and propagation mechanisms. This is essential to allow targeted elimination of cancer cells without altering normal mitotic cells. Currently, there are two main rival theories describing the process of tumorigenesis. According to the Stochastic Model, potentially any cell, once defunct, is capable of initiating carcinogenesis. Alternatively the Cancer Stem Cell (CSC) Model posits that only a small fraction of undifferentiated tumor cells are capable of triggering carcinogenesis. Like healthy stem cells, CSCs are also characterized by a capacity for self-renewal and the ability to generate differentiated progeny, possibly mediating treatment resistance, thus leading to tumor recurrence and metastasis. Moreover, molecular signaling profiles are similar between CSCs and normal stem cells, including Wnt, Notch and Hedgehog pathways. Therefore, development of novel chemotherapeutic agents and proteins (e.g., enzymes and antibodies) specifically targeting CSCs are attractive pharmaceutical candidates. This article describes small molecule inhibitors of stem cell pathways Wnt, Notch and Hedgehog, and their recent chemotherapy clinical trials.