A multifaceted role of bisphosphonates from palliative care to anti-cancer therapy in solid tumors.

INTRODUCTION: Bisphosphonates (P-C-Ps) also called diphosphonates are the structural analogs of naturally occurring pyrophosphates. Bisphosphonates are traditionally used and shown to provide long-term success in the treatment and prevention of osteoporosis and other bone loss pathologies. Furthermore, bisphosphonates are gaining popularity in the present era of cancer therapeutics and prevention. The usage of bisphosphonates as adjuvant or neoadjuvant therapy, either as a single agent or combined with other chemotherapy, has been studied in different solid tumors. This review aims to present the various roles of bisphosphonates in solid tumors. DATA SOURCES: Articles in MEDLINE/PubMed and the National Institutes of Health Clinical Trials Registry (http://www. Clinicaltrials.gov) between 1 January 2011 and 1 February 2022 were extracted using MeSH terms "bisphosphonates/diphosphosphonates and mechanism," "bisphosphonates and breast cancer," "bisphosphonates and prostate cancer," "bisphosphonates and lung cancer," "bisphosphonates and cancer risk," and "bisphosphonates and adverse events." Manual searches of some major oncology journals were also conducted. DISCUSSION: This review article focuses on the antitumor activity of bisphosphonates, safety profile, and the role of bisphosphonates as preventive, neoadjuvant, and adjuvant chemotherapy. A significant improvement in overall survival and cancer-specific survival and recurrence-free survival with the usage of bisphosphonates is noted in breast cancer patients, particularly in post-menopausal women. Though great progress has been achieved in over 20 years, further research is needed to identify the subgroup of patients that are most likely to benefit from adjuvant bisphosphonate therapy and to determine regimens with greater efficacy and better safety profile.

HOTAIR: a potential metastatic, drug-resistant and prognostic regulator of breast cancer.

HOX transcript antisense intergenic RNA (HOTAIR) is an oncogenic non-coding RNA whose expression is strongly correlated with the tumor grade and prognosis of a variety of carcinomas including breast cancer (BC). HOTAIR regulates various target genes via sponging and epigenetic mechanisms and controls various oncogenic cellular and signaling mechanisms including metastasis and drug resistance. In BC cells, HOTAIR expression is regulated by a variety of transcriptional and epigenetic mechanisms. In this review, we describe the regulatory mechanisms that govern HOTAIR expression during cancer development and explore how HOTAIR drives BC development, metastasis, and drug resistance. In the final section of this review, we focus on the role of HOTAIR in BC management, therapeutic treatment, and prognosis, highlighting its potential therapeutic applications.

Diffuse Large B-Cell Lymphoma of the Colon in an Asymptomatic Patient.

Extranodal lymphomas of the gastrointestinal (GI) tract are known entities, but primary lymphoma of the colon is extremely rare. Symptoms are non-specific, such as abdominal pain, bloody diarrhea, unintentional weight loss, night sweats, and changes in bowel habits. Some patients do not have any specific symptoms, which makes diagnosis extremely difficult. We present a 69-year-old asymptomatic male who was incidentally found to have an inflammatory mass in the descending colon on screening colonoscopy; the initial biopsy was inconclusive. However, due to high suspicion of any underlying malignancy, a repeat colonoscopy with biopsy was done, which revealed diffuse large B-cell lymphoma (DLBCL). Prompt and early diagnosis is extremely crucial for timely management. Management includes chemotherapy, radiotherapy, and surgery.

Nanoparticles mediated tumor microenvironment modulation: current advances and applications.

The tumor microenvironment (TME) plays a key role in cancer development and emergence of drug resistance. TME modulation has recently garnered attention as a potential approach for reprogramming the TME and resensitizing resistant neoplastic niches to existing cancer therapies such as immunotherapy or chemotherapy. Nano-based solutions have important advantages over traditional platform and can be specifically targeted and delivered to desired sites. This review explores novel nano-based approaches aimed at targeting and reprogramming aberrant TME components such as macrophages, fibroblasts, tumor vasculature, hypoxia and ROS pathways. We also discuss how nanoplatforms can be combined with existing anti-tumor regimens such as radiotherapy, immunotherapy, phototherapy or chemotherapy to enhance clinical outcomes in solid tumors.

A Case of Thrombotic Microangiopathy Secondary to Hypertensive Emergency.

Hypertension causing thrombotic microangiopathy (TMA) is one of the several etiologies of TMA, which causes endothelial damage and thrombosis of microvasculature, leading to hemolytic anemia, thrombocytopenia, and ischemic organ damage. Renal microvasculature involvement leading to renal dysfunction is most frequently seen in TMA but the degree of dysfunction varies with etiology. If left untreated, TMA carries a risk of high mortality, so it is extremely important for early identification of the cause of TMA. Plasma exchange is a commonly used treatment modality for TMA; however, it is not always necessary. Hypertension-induced TMA can be safely treated with antihypertensives, without the need for invasive plasma exchange. We report a 37-year-old African American hypertensive lady presenting with hypertensive emergency and TMA with rapidly progressing renal dysfunction. The patient had improvement in her platelet count after her blood pressure was reduced in a controlled manner.

A Rare Case of Colo-Colonic Intussusception Caused by Colonic Submucosal Lipoma.

Unlike in infancy, where intussusception is an abdominal emergency, diagnosis of intussusception could be tricky in adults as most of these patients present sub-acutely with vague abdominal symptoms. Early diagnosis could impact these patients significantly in decreasing morbidity and mortality along with reduction in healthcare expenses. Colo-colonic intussusception is rare and accounts for less than 20% of adult intussusception. More than 50% of adult intussusception is caused by mass-like lesions. In such cases, this could be an early presentation of malignant intestinal lesions. Abdominal CT is mandatory in all adult patients; when combined with ultrasound, it has 95.5% accuracy of pre-operative diagnosis. Here we report a case of a 42-year-old female who presented with a two-month history of intermittent abdominal pain; a CT abdomen revealed colo-colonic intussusception which was initially missed on prior imaging. We discuss the importance of considering intussusception as a rare differential of abdominal pain, the need for early diagnosis, and the role of colonoscopy and non-surgical management in adults.

Poly Adenosine Diphosphate-Ribose Polymerase (PARP) Inhibitors in Pancreatic Cancer.

Pancreatic cancer is the third most common cause of cancer death in the United States and eleventh worldwide. The majority of patients present with advanced disease with five-year overall survival of less than 10%. Traditional chemotherapy has been the mainstay treatment for years, with limited improvement in survival. Relative success has been achieved with agents targeting the DNA damage repair (DDR) mechanisms with poly adenosine diphosphate-ribose polymerase (PARP) inhibitors. The initial benefit was observed in patients with germline breast cancer-associated (BRCA) mutations. Multiple trials are now underway exploring PARP inhibitors in other DDR mutations such as the ataxia-telangiectasia mutated (ATM) gene and the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene (familial atypical multiple mole and melanoma syndrome), mismatch repair genes (Lynch syndrome), and others. PARP inhibitors are being evaluated as a single agent or combination chemotherapy, immunotherapy, and maintenance after chemotherapy. Here, we review current clinical trials targeting various DDR mutations and treatment strategies.

Targeting T regulatory cells: Their role in colorectal carcinoma progression and current clinical trials.

Colorectal cancer (CRC) is classified as the third leading cancer globally and one of the major causes of morbidity and mortality around the world. The interaction of the immune system with the cancer cells plays a vital role in CRC progression. Regulatory T cells (Tregs) are a form of T cells, which regulate and suppress unwanted activation of the immune system and play a major role in preventing autoimmune diseases. Tregs exhibit a significant role in immune modulation during CRC progression through accumulation in the tumor microenvironment (TME) and suppression of immunity against tumor specific antigens promoting tumor progression. The role of Tregs in CRC progression and its interaction with other immune cells within CRC TME and current clinical trials were reviewed in this paper.

Secondary Hemophagocytic Lymphohistiocytosis in a Post-COVID-19 Patient.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition caused by excessive immune system activation. HLH can be primary or secondary. Primary HLH is commonly seen in children with underlying genetic mutations, while secondary HLH can be seen at any age. It is usually triggered by inciting factors such as viral infections, patients with underlying rheumatological disease, or malignancies. It has very poor prognosis if left untreated, with survival of only a few months. While there have been around 100 cases of HLH reported during the acute phase of COVID-19 infection, very few post-COVID-19 HLH cases have been reported, only around 35 cases. Here we report a case of a 20-year-old Caucasian male who presented eight weeks after COVID-19 infection with extreme fatigue, fever, lab work concerning for HLH, and a high H score indicating a high probability of HLH. Early identification of HLH following COVID-19 recovery would allow for timely management of the condition.

Atypical Hemolytic Uremic Syndrome Caused by a Rare Complement Factor B Mutation.

Thrombotic microangiopathy (TMA), a rare and diagnostically challenging condition, commonly presents with a triad of thrombocytopenia, hemolytic anemia, and end-organ damage, such as renal failure. Most cases of the hemolytic uremic syndrome (HUS) are mediated by Shiga toxin-producing Escherichia coli, but some cases present as an atypical HUS, which includes thrombotic thrombocytopenic purpura and complement-mediated thrombotic microangiopathy (C-TMA). Although C-TMA occurs because of genetic and acquired mutations in the complement regulatory factors, it is usually hereditary. The currently available treatment options include therapeutic plasma exchange and administration of eculizumab, which is a monoclonal antibody against C5. Here, we report a diagnostically challenging and extremely rare case of a middle-aged Caucasian man who was diagnosed with atypical HUS that was caused by a mutation in complement factor B. This case highlights the importance of not overlooking rare causes of TMAs because the diagnostic evaluation is important for guiding appropriate management and obtaining a favorable prognosis.