Potentiation of Anticancer Activity of G₂/M Blockers by Mild Hyperthermia

Abstract

Background/Aim: Hyperthermia (HT), combined with chemotherapy, has been used to treat various types of cancer. This study aimed to investigate the HT-sensitivity of malignant and non-malignant cells, and then evaluate the combination effect of docetaxel (DTX) and a newly synthesized chromone derivative (compound A) with HT. Materials and Methods: The number of viable cells was determined using the MTT method. Cell cycle distribution was analyzed using a cell sorter, and DNA fragmentation pattern was detected using agarose gel electrophoresis. Results: Among 12 cultured cells, oral squamous cell carcinoma (OSCC), especially Ca9-22 cells, and myelogenous leukemia cells showed higher sensitivity to HT than lung carcinoma and glioblastoma cell lines, while normal oral cells were the most resistant. Cytotoxicity of DTX on Ca9-22 cells was maximum at 41-42˚C and 45~60 min exposure to HT. DXT, compound A, and HT induced G 2 /M arrest of Ca-22 cells. Mild HT enhanced the DTX-and compound A-induced subG 1 arrest, in a synergistic fashion. Conclusion: The combination G 2 /M blockers and mild-HT can potentially be used for the treatment of OSCC.Surgery, radiation, and chemotherapy are three standard treatments for oral cancer. Considering the postoperative impairment of physical function and appearance, minimally invasive therapies such as chemotherapy combined with hyperthermia (HT), which induces cancer cell death by heating to 42.5˚C or higher (1, 2), are promising. Treatment of malignant tumors with HT in Japan has long track record since the approval of insurance coverage in 1990. While chronic myelogenous leukemia cells have been reported to be highly sensitive to HT (3,4), clinical reports of HT on oral cancer have been limited. For HT, cancerous tissue is placed between two electrodes, and then is exposed to Joule heat generated using the radiofrequency dielectric warming method. This method is applicable to breast cancer that can be easily clamped between the electrodes, but not to primary tumor such as oral cancer (especially tongue cancer, which moves involuntarily). Therefore, HT for head and neck cancer, including oral cancer, is generally applied to cervical lymph node metastasis rather than the primary tumor (5). We have reported favorable clinical data of superselective intraarterial chemoradiotherapy (based of cisplatin, docetaxel (DTX) and radiation) for patients with oral squamous cell carcinoma with lymph node metastasis (6). In addition to the direct application to tumor, combination of relatively lower temperature for HT (41-42˚C) [mild hyperthermia (mild-HT)] have been reported (7, 8).

Effect of hyperthermia on intestinal microecology, immune function, and progression-free survival in patients with advanced unresectable lung adenocarcinoma

“…These findings suggest that hyperthermia has the potential to enhance the abundance and diversity of gut microbiota in lung cancer patients. Furthermore, animal model studies have demonstrated the direct impact of gut microbes on the response to immunotherapy 23 , 24 , 33 , 34 . In studies conducted on cancer patients undergoing immunotherapy, it has been observed that higher microbial diversity is associated with improved survival rates 25 , 26 .…”

“…Additionally, studies have shown that specific intestinal flora, such as Clostridiaceae and Ruminococcaceae, can accelerate the breakdown of estrogen in the intestine through the production of β-glucuronidase. This leads to higher levels of free estrogen, potentially contributing to the development of breast tumors 25 , 33 . On the other hand, the phylum Cyanobacteria and the phylum Reciprocal Bacteria, which are normally present in low numbers in the human body, exhibit a significant increase in lung cancer progression.…”

A Mini‐Review on the Application of Computational Strategies in Multi‐Armed Star‐PEG Polymeric Micelles for Drug Delivery

“…AI techniques facilitate the prediction of in vivo responses, the pharmacokinetics of new drugs, including their QSPR or QSAR, the determination of appropriate dosing, and the assessment of skin or blood-brain barrier permeability. [113][114][115][116][117][118][119][120] The use of in silico technologies has the potential to improve the efficiency and cost-effectiveness of drug discovery by facilitating the prediction of pharmacokinetic profiles of drug candidates, which is a critical aspect. [121] In the present scenario, machine learning methods such as the support vector process, Gaussian process, random forest, k closest neighbours, classification and regression tree, or Naive Bayes Classifier could prove beneficial.…”