Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that are involved in crucial aspects of cancer biology, including angiogenesis, cell survival, glucose metabolism and invasion. Intratumoral hypoxia and genetic alterations can lead to HIF-1alpha overexpression, which has been associated with increased patient mortality in several cancer types. In preclinical studies, inhibition of HIF-1 activity has marked effects on tumour growth. Efforts are underway to identify inhibitors of HIF-1 and to test their efficacy as anticancer therapeutics.

Targeting HIF-1 for cancer therapy

CA : A Cancer Journal for Clinicians

The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.

https://jcp.bmj.com/content/jclinpath/55/4/244.full.pdf

The causal relation between human papillomavirus and cervical cancer

Transitions between epithelial and mesenchymal states have crucial roles in embryonic development. Emerging data suggest a role for these processes in regulating cellular plasticity in normal adult tissues and in tumours, where they can generate multiple, distinct cellular subpopulations contributing to intratumoural heterogeneity. Some of these subpopulations may exhibit more differentiated features, whereas others have characteristics of stem cells. Owing to the importance of these tumour-associated phenotypes in metastasis and cancer-related mortality, targeting the products of such cellular plasticity is an attractive but challenging approach that is likely to lead to improved clinical management of cancer patients.

Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits

The molecular mechanisms that underlie tumour progression are still poorly understood, but recently our knowledge of particular aspects of some of these processes has increased. Specifically, the identification of Snail, ZEB and some basic helix-loop-helix (bHLH) factors as inducers of epithelial-mesenchymal transition (EMT) and potent repressors of E-cadherin expression has opened new avenues of research with potential clinical implications.

Snail, ZEB and bHLH factors in tumour progression: an alliance against the epithelial phenotype?

Background: Patients undergoing prophylactic central compartment dissection (CLND) for papillary thyroid cancer (PTC) are often overtreated. Molecular fluorescence-guided imaging (MFGI) and spectroscopy may be useful for the detection of PTC nodal metastases (NM) and to identify negative central compartments intraoperatively. This study aims to identify a PTC-specific antigen targeted by a clinical available near infrared fluorescent (NIRF)-tracer; associate protein overexpression of the selected antigen with locoregional recurrence rates; assess selective binding of the selected NIRF-tracer in vitro and evaluate safety and efficacy of the selected NIRF-tracer for the detection of PTC NM using MFGI and quantitative spectroscopy in humans. 

MET Targeted Molecular Fluorescence Guided Imaging and Quantitative Spectroscopy for the Detection of Lymph Node Metastases in Papillary Thyroid Cancer

Abstract Background The role of duct excision surgery is not clearly defined in patients with pathological nipple discharge without other clinical and radiological abnormalities. The primary aim of this systematic review was to determine the malignancy rate in patients with pathological nipple discharge after duct excision surgery (microdochectomy/major duct excision). The secondary aims were to determine the recurrence rate of pathological nipple discharge after surgery and to assess breast cancer development after surgery. Methods MEDLINE and Embase were searched from inception to March 2023, using search terms related to ‘nipple discharge’, ‘nipple fluid’, ‘microdochectomy’, ‘duct excision’, and ‘minimally invasive surgical procedure’. Studies reporting data about women who underwent duct excision surgery for pathological nipple discharge without clinical and radiological suspicion of breast cancer, as well as reporting data on women diagnosed with breast cancer after duct excision surgery, were included. Results A total of 318 titles were identified, of which nine publications were included in the analysis. This resulted in 1108 patients with pathological nipple discharge who underwent a duct excision. The weighted mean rate of malignancy after duct excision surgery was 8.1 per cent (ranging from 2.3 to 13.5 per cent). Three studies described the recurrence rate of pathological nipple discharge (ranging from 0 to 12 per cent) and two studies reported breast cancer development in the follow-up in a total of three patients (less than 1 per cent). Conclusion The malignancy rate after duct excision surgery for pathological nipple discharge was low in patients with pathological nipple discharge without radiological and clinical abnormalities and approximately 9 of 10 patients undergo surgery for a benign cause. Improvement of the diagnostic and therapeutic workup is needed to prevent patients from undergoing (unnecessary) exploratory surgery.

Role of duct excision surgery in the treatment of pathological nipple discharge and detection of breast carcinoma: systematic review

This chapter provides an up-to-date discussion of the virtues and flaws of these different methods and to present practical guidelines for the sentinel node (SN) investigation in gynecologic cancers. Accurate and efficient intraoperative assessment of the SN by the pathologist may be done by frozen-section analysis, usually a single hematoxylin and eosin (H&amp;E) frozen section. Imprint slides can simply be produced from lymph nodes by firmly pressing the cut surface to a glass slide. In a postoperative and intraoperative setting, the May-Grünwald-Giemsa and Quickdiff stains, respectively, allow detection of metastatic cells. The SNs are fixed in neutral buffered formaldehyde and completely embedded after lamellating them according to their size. A few studies have explored the possibility of ultrasonographically guided fine-needle aspiration biopsy (FNAB) to detect SN metastases. Flow cytometry (FCM) is a technique of measuring the properties of cells in suspension after staining with a fluorescent dye. 

Ultrastaging of the sentinel node

Confocal Laser Scanning Microscopy provides the opportunity to perform 3-D DNA content measurements on intact cells in thick histological sections. The aim of this study was to describe the conditions for accurate and fast 3-D CLSM cytometry with a minimum of user interaction to arrive at sufficient throughput for pilot clinical applications. To achieve this aim, nuclear DNA was stained in 14 μm thick tissue sections of normal liver and adrenal stained with either YOYO-1 iodide or TO-PRO-3 iodide. Different pre-treatment strategies were evaluated: boiling in citrate buffer (pH 6.0) followed by RNase application for 1 or 18 hours, or hydrolysis. The image stacks obtained with CLSM at microscope magnifications of ×40 or ×100 were analyzed off-line using in-house developed software for semi-automated 3-D fluorescence quantification. As a measure of histogram quality, the coefficient of variation (CV) of the diploid peak was assessed. The lowest CV (10.3%) was achieved with a protocol without boiling, with 1 hour RNase treatment and TO-PRO-3 iodide staining, and a final image recording at ×60 or ×100 magnifications. A sample size of 300 nuclei was generally achievable. By filtering the set of automatically segmented nuclei based on volume, size and shape, followed by interactive removal of the few remaining faulty objects, a single measurement was completely analyzed in approximately 3 hours. The described methodology allows obtaining a largely unbiased sample of nuclei in thick tissue sections using 3-D DNA cytometry by confocal laser scanning microscopy within an acceptable time frame for pilot clinical applications, and with a CV small enough to resolve small near diploid stemlines. Andre Huisman (2006) 3-D Nuclear chromatin texture analysis using confocal laser scanning microscopy

/pdf/implementation-of-accurate-and-fast-dna-cytometry-2a9i5j22ab.pdf

Paul J. van Diest

Papers

MET Targeted Molecular Fluorescence Guided Imaging and Quantitative Spectroscopy for the Detection of Lymph Node Metastases in Papillary Thyroid Cancer

Role of duct excision surgery in the treatment of pathological nipple discharge and detection of breast carcinoma: systematic review

Ultrastaging of the sentinel node

Implementation of accurate and fast DNA cytometry

In Reply to Tsoutsou.