Extracellular Vesicles as Liquid Biopsy Biomarkers across the Cancer Journey: From Early Detection to Recurrence.

BACKGROUND: Cancer is a dynamic process and thus requires highly informative and reliable biomarkers to help guide patient care. Liquid-based biopsies have emerged as a clinical tool for tracking cancer dynamics. Extracellular vesicles (EVs), lipid bilayer delimited particles secreted by cells, are a new class of liquid-based biomarkers. EVs are rich in selectively sorted biomolecule cargos, which provide a spatiotemporal fingerprint of the cell of origin, including cancer cells. CONTENT: This review summarizes the performance characteristics of EV-based biomarkers at different stages of cancer progression, from early malignancy to recurrence, while emphasizing their potential as diagnostic, prognostic, and screening biomarkers. We discuss the characteristics of effective biomarkers, consider challenges associated with the EV biomarker field, and report guidelines based on the biomarker discovery pipeline. SUMMARY: Basic science and clinical trial studies have shown the potential of EVs as precision-based biomarkers for tracking cancer status, with promising applications for diagnosing disease, predicting response to therapy, and tracking disease burden. The multi-analyte cargos of EVs enhance the performance characteristics of biomarkers. Recent technological advances in ultrasensitive detection of EVs have shown promise with high specificity and sensitivity to differentiate early-cancer cases vs healthy individuals, potentially outperforming current gold-standard imaging-based cancer diagnosis. Ultimately, clinical translation will be dictated by how these new EV biomarker-based platforms perform in larger sample cohorts. Applying ultrasensitive, scalable, and reproducible EV detection platforms with better design considerations based upon the biomarker discovery pipeline should guide the field towards clinically useful liquid biopsy biomarkers.

Laron Syndrome: A Tale of Two Siblings.

Primary growth hormone (GH) resistance or growth hormone insensitivity syndrome, also called Laron syndrome, is a hereditary disease caused by mutations in the GH receptor or in the post-receptor signaling pathway. This disorder is characterized by postnatal growth failure resembling GH deficiency. Differentiating the two conditions is necessary. We present the cases of two siblings, a 16-year-old female and a 9-year-old male, born from a consanguineous union. Both had normal birth weights with subsequent severe short stature and delayed teeth eruption, with no features suggestive of any systemic illness. Serum insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) were both low. Suspecting GH deficiency, provocative testing with clonidine was done revealing peak growth hormone >40 ng/mL in both patients. In view of low IGF1 and IGFBP3 and high GH on stimulation, IGF1 generation test was done for both siblings, with values supporting the diagnosis of GH insensitivity or Laron syndrome.

Translating Molecular Biology Discoveries to Develop Targeted Cancer Interception in Barrett's Esophagus.

Esophageal adenocarcinoma (EAC) is a rapidly increasing lethal tumor. It commonly arises from a metaplastic segment known as Barrett's esophagus (BE), which delineates the at-risk population. Ample research has elucidated the pathogenesis of BE and its progression from metaplasia to invasive carcinoma; and multiple molecular pathways have been implicated in this process, presenting several points of cancer interception. Here, we explore the mechanisms of action of various agents, including proton pump inhibitors, non-steroidal anti-inflammatory drugs, metformin, and statins, and explain their roles in cancer interception. Data from the recent AspECT trial are discussed to determine how viable a multipronged approach to cancer chemoprevention would be. Further, novel concepts, such as the repurposing of chemotherapeutic drugs like dasatinib and the prevention of post-ablation BE recurrence using itraconazole, are discussed.

Os(II) complexes for catalytic anticancer therapy: recent update.

The recent dramatic enhancement in cancer-related mortality and the drawbacks (side effects and resistance) of Pt-based first-generation chemotherapeutics have escalated the need for new cancer medicines with unique anticancer activities for better human life. To overcome the demerits of Pt-based cancer drugs, the concept of catalytic anticancer agents has recently been presented in the field of anticancer metallodrug development research. Many intracellular transformations in cancer cells are catalyzed by metal complexes, including pyruvate reduction to lactate, NAD(P)+ reduction to NAD(P)H and vice versa, and the conversion of 3O2 to reactive oxygen species (ROS). These artificial in-cell changes with non-toxic and catalytic dosages of metal complexes have been shown to disrupt several essential intracellular processes which ultimately cause cell death. This new approach could develop potent next-generation catalytic anticancer drugs. In this context, recently, several 16/18 electron Os(II)-based complexes have shown promising catalytic anticancer activities with unique anticancer mechanisms. Herein, we have delineated the catalytic anticancer activity of Os(II) complexes from a critical viewpoint. These catalysts are reported to induce the in-cell catalytic transfer hydrogenation of pyruvate and important quinones to create metabolic disorder and photocatalytic ROS generation for oxidative stress generation in cancer cells. Overall, these Os(II) catalysts have the potential to be novel catalytic cancer drugs with new anticancer mechanisms.

Leydig Cell Hyperplasia of Ovary - An Unusual Finding in Postneoadjuvant Chemotherapy Case of Primary Fallopian Tube Carcinoma.

A large number of high-grade serous ovarian carcinomas originate in the fallopian tubes. Neoadjuvant chemotherapy followed by surgery may lead to a number of chemotherapy-induced changes in the ovary, which may lead to an erroneous diagnosis. We present a rare case of a 55-year-old postmenopausal woman who was clinically diagnosed with carcinoma of the right ovary; on histopathologic evaluation after neoadjuvant chemotherapy, the primary site was found to be the right fallopian tube. The right ovary showed chemotherapy-related changes along with extensive Leydig cell hyperplasia. As the presence of Leydig cell hyperplasia in this setting is an unusual finding, it may pose a diagnostic dilemma for the pathologist; so an awareness of this entity is important to avoid misdiagnosis.

Crystallising galactocele of the breast: a rare cytological diagnosis.

Galactocele of the breast is a benign condition characterised by milk containing cystic lesions, usually present during pregnancy and lactation. The diagnosis of galactocele is difficult due to physiological changes which occur during pregnancy and lactation. Fine needle aspiration cytology proves to be a simple and minimally invasive procedure in diagnosing and treating this condition. Very rarely, long-standing galactoceles can show crystal formation on aspirate smears, termed as crystallising galactocele. Herein, we present this rare case of crystallising galactocele in a 26-year-old lactating woman. We are reporting this case because of its rarity, as less than 10 cases have been reported so far.

Is Priapism a Common Presentation of Chronic Myeloid Leukemia in an Adolescent Patient?

Chronic myeloid leukemia (CML) is predominantly a disease of adults and the elderly. CML is uncommon in the paediatric age. Priapism as an initial presentation is quite uncommon in CML and is rare in the case of CML in paediatric and adolescent age. We present a case of CML in an adolescent male who presented with priapism of 48 hours duration. The patient was managed in an emergency by corporal aspiration and saline irrigation and was found to have CML during a hospital stay. The patient was treated with imatinib and is under follow-up for the last two years.

Gallbladder Tuberculosis Presenting as Obstructive Jaundice.

Isolated gallbladder tuberculosis is a rare entity, even in endemic zones. Preoperative diagnosis is usually not possible, with most of the cases being diagnosed either as cholecystitis or malignancy. Histopathological examination of the resected specimen clinches the diagnosis. We present a middle-aged man with obstructive jaundice who was diagnosed to have gallbladder malignancy clinically and radiologically and on microscopy, and was diagnosed as gallbladder tuberculosis with the involvement of the common bile duct.