Klavuzons are 6-(naphthalen-1-yl) substituted 5,6-dihydro-2H-pyran-2-one derivatives showing promising antiproliferative activities in variety of cancer cell lines. In this work, racemic syntheses of nine novel 4'-alkyl substituted klavuzon derivatives were completed in eight steps and anticancer properties of these compounds were evaluated. It is found that size of the substituent has dramatic effect over the potency and selectivity of the cytotoxic activity in cancerous and healthy pancreatic cell lines. The size of the substituent can also effect the CRM1 inhibitory properties of klavuzon derivatives. Strong cytotoxic activity and CRM1 inhibition can be observed only when a small substituent present at 4'-position of naphthalen-1-yl group. However, these substituents makes the molecule more cytotoxic in healthy pancreatic cells rather than cancerous pancreatic cells. Among the tested compounds 1,2,3,4-tetrahydrophenanthren-9-yl substituted lactone was the most cytotoxic compound and its antiproliferative activity was also tested in 3D spheroids generated from HuH-7 cell lines.

Rectal cancer constitutes approximately one-third of all colorectal cancers and contributes to considerable mortality globally. In contrast to colon cancer, the standard treatment for localized rectal cancer often involves neoadjuvant chemoradiotherapy. Tumour response rates to treatment show substantial inter-patient heterogeneity, indicating a need for treatment stratification. Consequently researchers have attempted to establish new means for predicting tumour response in order to assist in treatment decisions. In this review we have summarized published findings regarding potential biomarkers to predict neoadjuvant treatment response for rectal cancer tumours. In addition, we describe cell-based models that can be utilized both for treatment prediction and for studying the complex mechanisms involved.

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Background/aim Matrix metalloproteinases (MMPs) play an important role in the evaluation of many cancer types; however, the detection usually presents a challenge. Further assays for a better understanding of the fundamental roles of MMPs in pathophysiology are still needed. We aimed to use an activatable probe in scanning acoustic microscopy (SAM) to evaluate acoustically if the probe can aid the visualization of the effects of in vitro MMP activity. Materials and methods We applied scanning acoustic impedance microscopy to obtain acoustic impedance maps of the cell line models of HT1080, THP-1, and SK-MEL-28 with and without MMPSense 680 probe incubation. We visually validated our results using confocal laser scanning microscopy imaging. We further analyzed the effects of MMPSense 680 probe on cell viabilities to eliminate any artifacts. Results This is the first study presenting the applicability of SAM in the acoustical evaluation of MMPSense 680 probe cleavage in a cellular medium through acoustic impedance measurements. We proposed that SAM measurement with the activatable probe can be used as an effective tool for studying the acoustical variations of MMP activities in cell lines. As a result, we detected MMPSense 680 probe cleavage in HT1080 human fibrosarcoma cell line. Conclusion We showed that SAM with the smart probe can detect proteolytic activity using MMPSense 680 in in vitro HT1080 cell line by acoustic impedance measurements. SAM could be proposed as an alternative tool leading a novel way for a better understanding of the roles of MMPs in cancer progression before clinical settings.