Increased expression of Profilin potentiates chemotherapeutic agent-mediated tumour regression

Author(s):  
Shashank Saurav ◽  
Sunil Kumar Manna
2020 ◽  
Vol 4 (1) ◽  
pp. 17-29
Author(s):  
Isma Attique ◽  
Shabbir Hussain ◽  
Muhammad Amjad ◽  
Khalida Nazir ◽  
Muhammad Shahid Nazir

Fluorine has a useful positron transmitting isotope and it enjoys broad application in the medical field. It is utilized in fluorinated agents,therapeutic sciences and steroid field. Fluorine incorporation viafluoroalkylation is a useful approach in the development of new functional materials and in drug design. Fluorine also plays its role as an anticancer agent and is a successful chemotherapeutic agent for certain sorts of malignant growth. 5-fluorouracil plays a vital role in the treatment of cancer. 18 Facts as a radio label tracer atom in PET imaging. 19 F has the second most sensitive and stable NMR-active nucleus.


Submit Manuscript | http://medc rav eonline.co m Introduction Colorectal adenocarcinoma is the third most common malignant neoplasia and the third leading cause of death from cancer in men and women in the United States. Current data show that the incidence of colorectal adenocarcinoma is decreasing in developed countries but increasing in developing countries. 1 The 2018 estimates of the Bra - zilian National Cancer Institute (Instituto Nacional do Câncer–INCA) were 17,380 new cases in men and 18,980 in women, making col - orectal adenocarcinoma the third most common neoplasia in men and the second most common in women in Brazil. 2 In the past 15 years, rectal cancer management has evolved in several aspects. Specifical - ly, a better understanding of the natural history of the disease, more precise radiological staging, multimodal therapeutic intervention, refined surgical techniques, and more detailed histopathological re - ports may have positively influenced patient survival. In this context, multidisciplinary management of colorectal cancer plays an important role and requires the coordinated teamwork of colorectal surgeons, oncologists, radiologists, and radiotherapists. 3 Total mesorectal exci - sion is still the basis of treatment in rectal cancer. However, neoadju - vant therapy and more conservative practices have been adopted in cases of clinical/pathological responses to radiochemotherapy. 4 Ra - diological evaluation of the response is of paramount importance for the selection of patients eligible for alternative treatment strategies, including ‘watch-and-wait’. Diffusion-weighted imaging is already being used routinely in the evaluation of the pathological response of rectal tumour patients submitted to neoadjuvant therapy. Some re - searchers have tried to estimate the tumour regression grade (TRG) using magnetic resonance imaging, as has been described for post-ra - diochemotherapy pathological evaluation, thus rendering it a valuable instrument. Considering the good results obtained with multimodal therapy in extraperitoneal rectal cancer, the evaluation of the pathological re - sponse post-neoadjuvant therapy must be considered as a factor for safe indication, both for the conservative option, in which the organ is preserved, and for radical surgical resection, influencing the choice between sphincter-preserving surgery and abdominoperineal excision. A precise evaluation, by comparing the results of post-neoadjuvant therapy magnetic resonance imaging with those obtained from his - Int J Radiol Radiat Ther. 2018;5(4):254 ‒ 258. 254 © 2018 Oliveira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and build upon your work non-commercially. Magnetic resonance imaging is effective in assessing tumour regression after neoadjuvancy in rectal adenocarcinoma

Author(s):  
Fábio Henrique de Oliveira ◽  
Antônio Lacerda-Filho ◽  
Fábio Lopes de Queiroz ◽  
Tatiana Martins Gomide Leite ◽  
Paulo Guilherme Oliveira Sales ◽  
...  

2007 ◽  
Vol 30 (4) ◽  
pp. 39 ◽  
Author(s):  
D. S. Hayre

William Coley, a young surgeon at New York Memorial Hospital, was traumatized by the loss of his first patient to bone cancer in 1891. He was unable to save this young patient and she succumbed to her Sarcoma within 3 months of surgery. He searched the hospital archive to learn more about Sarcoma and discovered the case of a patient with a large sarcoma who had undergone five unsuccessful surgeries over a 3 year period. This case had been determined to be hopeless. After the last of these operations, the patient became very ill from an erysipelas infection. Coley was astonished to read that after the fever broke and the patient had recovered, the tumour had vanished. Seven years later, the patient was still alive and well. Coley concluded that whatever had caused the fever must also have destroyed the cancer. Coley searched for and found this patient still in excellent health. Coley reasoned that if a chance infection could make tumours vanish, then a purposefully induced infection could do the same. The hypothesis was tested by infecting his next 10 patients with Streptococcus pyogenes to cause Erysipelas. Some of the patients were difficult to infect, some died, and some had a strong reaction and their disease regressed. Coley switched to deactivated S. pyogenes to avoid the mortality observed with the live strain. Afterxperimentation with various formulations, a combination of S pyogenes and Serratia marcescens was decided upon and became known as Coley’s Toxin. The preferred method of delivery was injection of the toxin directly into the primary tumour or metastases in increasing doses to avoid immune tolerance. Fever response in the patient was essential to imitate a naturally occurring infection and the body’s natural response. Though Coley met with success, this therapy was abandoned as chemotherapy became more popular. Hoption Cann SA, Gunn HD, van Netten JP, van Netten C. Dr William Coley and tumour regression: a place in history or in the future. Post Graduate Medical Journal 2003; 79:672-680. Hobohm U. Fever and Cancer in Perspective. Cancer Immunology & Immunotherapy 2001; 50:391-396. Grange JM, Standord JL, Stanford CA. Campbell De Morgan’s ‘Observations on cancer’, and their relevance today. Journal of the Royal Society of Medicine 2002 (June); 95:296-299.


2018 ◽  
Vol 25 (36) ◽  
pp. 4758-4784 ◽  
Author(s):  
Amy L. Wilson ◽  
Magdalena Plebanski ◽  
Andrew N. Stephens

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.


2019 ◽  
Vol 24 (36) ◽  
pp. 4312-4333 ◽  
Author(s):  
Eva M. Domínguez-Martín ◽  
Ana M. Díaz-Lanza ◽  
Célia M. C. Faustino

The exponential growth of cancer cases worldwide together with recent advances concerning the pathophysiological mechanisms of the disease at the molecular level led to a paradigm shift in chemotherapy, from monotherapy to targeted drug combination regimens. However, adverse effects and the emergence of multidrug resistance (MDR) limit the effectiveness of these therapies. In this context, hybrid combinations mixing anticancer drugs and bioactive phytochemical components from medicinal plants, or even plant extracts, that can act synergistically on multiple targets and signaling pathways represent a promising approach with the potential to expand the current therapeutic arsenal. This review aims to provide a synopsis on anticancer hybrid combinations based on their multi-target mechanisms and synergistic effects from an extensive literature search focusing mainly on publications from the last ten years. In most of these combinations, the phytochemical component was shown to enhance the anticancer activity of the chemotherapeutic agent and to sensitize chemoresistant tumors in several types of cancer. Hybrid combinations, due to synergistic interactions, are also associated with less severe adverse events since lower doses can be used to achieve the same therapeutic effect. Further preclinical and clinical studies are needed, as well as the development of an adequate regulatory framework, before hybrid combination therapy can be translated into clinical practice.


2018 ◽  
Vol 18 (7) ◽  
pp. 1054-1063 ◽  
Author(s):  
Ning Ding ◽  
Hong Zhang ◽  
Shan Su ◽  
Yumei Ding ◽  
Xiaohui Yu ◽  
...  

Background: Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure. Objective: Emodin is commonly used clinically to increase the sensitivity of chemotherapeutic agents, yet whether Emodin promotes the role of Cisplatin in the treatment of endometrial cancer has not been studied. Method: CCK-8 kit was utilized to determine the growth of two endometrial cancer cell lines, Ishikawa and HEC-IB. The apoptosis level of Ishikawa and HEC-IB cells was detected by Annexin V / propidium iodide double-staining assay. ROS level was detected by DCFH-DA and NADPH oxidase expression. Expressions of drug-resistant genes were examined by real-time PCR and Western blotting. Results: Emodin combined with Cisplatin reduced cell growth and increased the apoptosis of endometrial cancer cells. Co-treatment of Emodin and Cisplatin increased chemosensitivity by inhibiting the expression of drugresistant genes through reducing the ROS levels in endometrial cancer cells. In an endometrial cancer xenograft murine model, the tumor size was reduced and animal survival time was increased by co-treatment of Emodin and Cisplatin. Conclusion: This study demonstrates that Emodin enhances the chemosensitivity of Cisplatin on endometrial cancer by inhibiting ROS-mediated expression of drug-resistance genes.


2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i7-i7
Author(s):  
Jiaojiao Deng ◽  
Sophia Chernikova ◽  
Wolf-Nicolas Fischer ◽  
Kerry Koller ◽  
Bernd Jandeleit ◽  
...  

Abstract Leptomeningeal metastasis (LM), a spread of cancer to the cerebrospinal fluid and meninges, is universally and rapidly fatal due to poor detection and no effective treatment. Breast cancers account for a majority of LMs from solid tumors, with triple-negative breast cancers (TNBCs) having the highest propensity to metastasize to LM. The treatment of LM is challenged by poor drug penetration into CNS and high neurotoxicity. Therefore, there is an urgent need for new modalities and targeted therapies able to overcome the limitations of current treatment options. Quadriga has discovered a novel, brain-permeant chemotherapeutic agent that is currently in development as a potential treatment for glioblastoma (GBM). The compound is active in suppressing the growth of GBM tumor cell lines implanted into the brain. Radiolabel distribution studies have shown significant tumor accumulation in intracranial brain tumors while sparing the adjacent normal brain tissue. Recently, we have demonstrated dose-dependent in vitro and in vivo anti-tumor activity with various breast cancer cell lines including the human TNBC cell line MDA-MB-231. To evaluate the in vivo antitumor activity of the compound on LM, we used the mouse model of LM based on the internal carotid injection of luciferase-expressing MDA-MB-231-BR3 cells. Once the bioluminescence signal intensity from the metastatic spread reached (0.2 - 0.5) x 106 photons/sec, mice were dosed i.p. twice a week with either 4 or 8 mg/kg for nine weeks. Tumor growth was monitored by bioluminescence. The compound was well tolerated and caused a significant delay in metastatic growth resulting in significant extension of survival. Tumors regressed completely in ~ 28 % of treated animals. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, Quadriga’s new agent could be effective as a therapeutic for both primary and metastatic brain tumors such as LM. REF: https://onlinelibrary.wiley.com/doi/full/10.1002/pro6.43


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