A perspective on emerging therapies in metastatic colorectal cancer: Focusing on molecular medicine and drug resistance.

The majority of cancer cases are colorectal cancer, which is also the second largest cause of cancer-related deaths worldwide. Metastasis is the leading cause of death for patients with colorectal cancer. Metastatic colorectal cancer incidence are on the rise due to a tiny percentage of tumors developing resistant to medicines despite advances in treatment tactics. Cutting-edge targeted medications are now the go-to option for customized and all-encompassing CRC care. Specifically, multitarget kinase inhibitors, antivascular endothelial growth factors, and epidermal growth factor receptors are widely used in clinical practice for CRC-targeted treatments. Rare targets in metastatic colorectal cancer are becoming more well-known due to developments in precision diagnostics and the extensive use of second-generation sequencing technology. These targets include the KRAS mutation, the BRAF V600E mutation, the HER2 overexpression/amplification, and the MSI-H/dMMR. Incorporating certain medications into clinical trials has significantly increased patient survival rates, opening new avenues and bringing fresh viewpoints for treating metastatic colorectal cancer. These focused therapies change how cancer is treated, giving patients new hope and better results. These markers can significantly transform and individualize therapy regimens. They could open the door to precisely customized and more effective medicines, improving patient outcomes and quality of life. The fast-growing body of knowledge regarding the molecular biology of colorectal cancer and the latest developments in gene sequencing and molecular diagnostics are directly responsible for this advancement.

An extract of the fern Polypodium leucotomos inhibits human peripheral blood mononuclear cells proliferation in vitro.

An alcoholic extract of the fern polypodium leucotomos (PLE) has been empirically used as an immunosuppressor for the treatment of several autoimmune diseases. In this paper, we investigated the effects of PLE on activation and proliferative responses of peripheral blood mononuclear cells (PBMNC) from healthy donors to T lymphocyte polyclonal mitogens. PLE shows a significant inhibitory effect on the proliferative response of PBMNC to stimulation with phytohaemagglutinin (PHA) or anti CD3 monoclonal antibodies (p < 0.05). In contrast, PLE did not modify the proliferative response of PBMNC to phorbol esters (p > 0.05). The inhibitory effect of PLE upon mitogen induced PBMNC proliferation is time dependent and can be overcome by the exogenous addition of interleukin-2 to the culture medium (p < 0.05). The decreased proliferative response of PBMNC to PHA stimulation in the presence of PLE is not associated with a significant modification of expression of the alpha chain (CD25) of the IL-2 receptor (p > 0.05). In conclusion, PLE shows an inhibitory effect on the polyclonal proliferative response of PBMNC to T lymphocyte mitogens that interact with cytoplasmic membrane molecules.

Therapeutic response of chronic active hepatitis B (CAHB) to a new immunomodulator: AM3. Immunohematological effects.

AM3, a biological response modifier (BRM) of polysaccharide/protein nature, was given by the oral route to 13 patients with chronic active hepatitis B (CAHB). After 12 months of daily treatment, 8 patients cleared serum HBV-DNA and HBeAg together with ALT normalization. Immunohaematologic studies showed how time of inhibition of viral replication was related to significant decreases of CD4, CD8 and B cell blood lymphocytes. After serum viral elimination, however, a significant haematologic rebound of peripheral blood mononuclear cells (PMNC): CD3, CD4 and CD8 lymphocytes was seen. These data, suggest that the antiviral activities of AM3 may be due to its immunodulatory capacities. These promising results, together with the absence of any side effects, justify the entry to trials with a larger number of patients. Furthermore, treatment with AM3 may help to elucidate the pathophysiology of CAHB.

[AM3 (a biological response modifier) in the treatment of recurrent aphthous stomatitis. Clinical evaluation and preliminary studies on NK (CD16) cells and their pathogenic role in the syndrome]. / AM3 (modificador de la respuesta biológica) en el tratamiento de la estomatitis aftosa recidivante. Valoración clínica y estudios preliminares sobre células NK (CD16) y su relación con la patogenia del síndrome.

In an open-controlled trial--oral washes (20 patients) versus test (19 patients)--, we have studied the effects of AM3 (a new oral BRM) on clinical evolution of the recurrent stomatitis (RAS) syndrome. The results obtained at 6th month showed significant decreases on ulcer numbers (p less than 0.001) as well as in their mean duration time (p less than 0.001) due to the AM3 treatment. From a pathophysiologic point of view, the study of the NK peripheral blood cells (Leu 11/CD16) suggests the existence of two kinds of RAS-patients: those showing normal NK cell numbers (approximately 33%) and those ones showing a partial lack in the NK numbers (approximately 67%). These results suggest different rational new approaches to treatment, based on new pathophysiological concepts.

Bone marrow recuperation by AM3 in breast cancer patients submitted to aggressive adjuvant treatment. A preliminary report.

The results of a prospective randomized study of 46 patients with breast carcinoma are presented. Twenty six patients were treated with AM3 (biological response modifier) associated with adjuvant radiotherapy and chemotherapy. Bone marrow hypoplasia was observed in 26.9% of the patients treated with AM3 compared with a 65% incidence in the control group (P less than 0.05). All patients showed leukopenia in peripheral blood count; however, the nadir of leukocytes was 4,000 leu/mm3 in the test group, compared with 1,900 leu/mm3 in the control group. None of the patients in the AM3 group showed thrombocytopenia, whereas 55% in the control group did. In none of the AM-3-treated cases was it necessary to modify the therapeutic schedule of adjuvant treatment.