Circulating tumor cells (CTCs) carried by the patient's bloodstream are known to lead to the metastatic spread of cancer. It is becoming increasingly clear that an understanding of the nanomechanical characteristics of CTCs, such as elasticity and adhesiveness, represents advancements in tracking and monitoring cancer progression and metastasis. In the present work, we describe a combined microfluidic-atomic force microscopy (AFM) platform that uses antibody-antigen capture to routinely isolate and nanomechanically characterize CTCs present in blood samples from prostate cancer patients. We introduce the reversible assembly of a microfluidic device and apply refined and robust chemistry to covalently bond antibodies onto its glass substrate with high density and the desired orientation. As a result, we show that the device can efficiently capture CTCs from patients with localized and metastatic prostate cancer through anti-EpCAM, anti-PSA, and anti-PSMA antibodies, and it is suitable for AFM measurements of captured intact CTCs. When nanomechanically characterized, CTCs originating from metastatic cancer demonstrate decreased elasticity and increased deformability compared to those originating from localized cancer. While the average adhesion of CTCs to the AFM tip surface remained the same in both the groups, there were fewer multiple adhesion events in metastatic CTCs than there were in their counterparts. The developed platform is simple, robust, and reliable and can be useful in the diagnosis and prognosis of prostate cancer as well as other forms of cancer.
In this work, for first time, circulating tumor cells (CTCs) are captured on an open biofunctionalized substrate with multiplexing capability. This is achieved by developing a new microfluidic probe (MFP) integrated with radially staggered herringbone (HB) elements for microvortex generation. The new tool, named as herringbone microfluidic probe (HB‐MFP), is a channel‐less microfluidic system with physically separated bottom capture substrate and top fluidics delivery system. The concept allows for functionalizing the capture substrate with multiple biorecognition ligands (in this work, stripes of different capture antibodies) and scanning the fluidics delivery system across the substrate in a 2D printing‐like movement. Using the HB‐MFP, CTCs are efficiently captured from prostate cancer blood samples through their specific EpCAM, PSMA, and PSA antigens in a single run, with counts ranging from as low as 6 CTCs mL‐1 (localized cancer patients) to as high as 280 CTCs mL‐1 (metastatic cancer patients). In the process, CTC clusters with sizes of as high as 40–50 cells are also successfully captured. The results indicate that multiplex profiles of CTCs could reveal certain cellular phenotypes based on PSMA and PSA expression levels. The developed HB‐MFP is simple and robust to use, allows for high throughput sample processing, and provides seamless access to captured CTCs for further downstream characterization.
IntroductionSymptomatic benign prostatic hyperplasia (BPH) is a condition that affects middle-aged men, leading to a decreased quality of life secondary to symptoms of difficult urination, urinary frequency, urgency and nocturia. The treatment modalities of this pathology include pharmacologic and invasive interventions, both of which vary in effectiveness and they come with a myriad of side effects. Recent advancements have allowed for the development of Rezum, a minimally invasive and effective approach to treating BPH while maintaining a good safety profile with comparable outcomes to other treatment modalities. MethodsWe retrospectively identified 49 patients with symptomatic BPH who underwent Rezum therapy in one center in Dubai, the United Arab Emirates between January and December 2020. We assessed several parameters related to their condition including prostate volume, pre-operative and post-operative post-void residual (PVR) and peak urinary flow (Qmax) number of treatments given, trial without catheter and mean date of follow-up. Safety and side effects were also assessed. ResultOur sample included symptomatic men with a mean age of 64 (10) who had a mean follow-up time of three months (IQR 2-5.2), median prostatic volume of 58 cc (IQR 44-82) and a mean of (SD 33.9). The initial Qmax and PVR were 7.3 ml/s (IQR 5.5-10.3) and 80.4 cm 3 (IQR 43.4-120.0) respectively, and post-operative Qmax and PVR were 16.3 ml/s (SD 5.7) and 20.7 cm 3 (IQR 16.2-28.2). Post-operatively, we observed a significant increase in Qmax of 8.11 ml/s (p=0.001) post-operatively, a mean decrease of 94.32 cm 3 (p=0.001) in PVR. The favorable outcome parameters in Qmax and PVR demonstrate the efficacy of this procedure. We have also noted that the change in Qmax and PVR does not vary by initial prostate volume. ConclusionIn this report, we aimed to highlight the benefit, efficacy and safety of offering Rezum to patients with symptomatic BPH in a single center in Dubai, reporting on the first United Arab Emirates experience with this novel procedure. This procedure confers the benefit of being minimally invasive, safe and effective, and with lower rates of sexual dysfunction compared to medical therapy or trans-urethral resection of the prostate (TURP). It is associated with similar outcomes to TURP, and an improvement in quality of life, while carrying a low-risk profile. Our experience corresponds with the available literature regarding the efficacy and satisfaction rates of Rezum for BPH patients. We hope that results from this study encourage further investigation into the long-term implications of Rezum, up to five years post-operatively.
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