There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Acute myeloid leukaemia (AML) is a disorder characterized by a clonal proliferation derived from primitive haematopoietic stem cells or progenitor cells. Abnormal differentiation of myeloid cells results in a high level of immature malignant cells and fewer differentiated red blood cells, platelets and white blood cells. The disease occurs at all ages, but predominantly occurs in older people (>60 years of age). AML typically presents with a rapid onset of symptoms that are attributable to bone marrow failure and may be fatal within weeks or months when left untreated. The genomic landscape of AML has been determined and genetic instability is infrequent with a relatively small number of driver mutations. Mutations in genes involved in epigenetic regulation are common and are early events in leukaemogenesis. The subclassification of AML has been dependent on the morphology and cytogenetics of blood and bone marrow cells, but specific mutational analysis is now being incorporated. Improvements in treatment in younger patients over the past 35 years has largely been due to dose escalation and better supportive care. Allogeneic haematopoietic stem cell transplantation may be used to consolidate remission in those patients who are deemed to be at high risk of relapse. A plethora of new agents - including those targeted at specific biochemical pathways and immunotherapeutic approaches - are now in trial based on improved understanding of disease pathophysiology. These advances provide good grounds for optimism, although mortality remains high especially in older patients.

Acute myeloid leukaemia.

The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study

Nanobodies as therapeutics: big opportunities for small antibodies

Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.

https://www.mdpi.com/1422-0067/19/1/195/pdf

Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review.

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family having tyrosine kinase activity. Dimerization of the receptor results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways leading to cell proliferation and tumorigenesis. Amplification or overexpression of HER2 occurs in approximately 15–30% of breast cancers and 10–30% of gastric/gastroesophageal cancers and serves as a prognostic and predictive biomarker. HER2 overexpression has also been seen in other cancers like ovary, endometrium, bladder, lung, colon, and head and neck. The introduction of HER2 directed therapies has dramatically influenced the outcome of patients with HER2 positive breast and gastric/gastroesophageal cancers; however, the results have been proved disappointing in other HER2 overexpressing cancers. This review discusses the role of HER2 in various cancers and therapeutic modalities available targeting HER2.

/pdf/human-epidermal-growth-factor-receptor-2-her2-in-cancers-4vb15z4wnj.pdf

Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications

Deregulated protein tyrosine kinase activity is central to the pathogenesis of human cancers. Targeted therapy in the form of selective tyrosine kinase inhibitors (TKIs) has transformed the approach to management of various cancers and represents a therapeutic breakthrough. Imatinib was one of the first cancer therapies to show the potential for such targeted action. Imatinib, an oral targeted therapy, inhibits tyrosine kinases specifically BCR-ABL, c-KIT, and PDGFRA. Apart from its remarkable success in CML and GIST, Imatinib benefits various other tumors caused by Imatinib-specific abnormalities of PDGFR and c-KIT. Imatinib has also been proven to be effective in steroid-refractory chronic graft-versus-host disease because of its anti-PDGFR action. This paper is a comprehensive review of the role of Imatinib in oncology.

https://downloads.hindawi.com/archive/2014/357027.pdf

Imatinib: A Breakthrough of Targeted Therapy in Cancer

Data on treatment outcome and prognostic factors in patients with metastatic soft tissue sarcoma (STS) are limited in the literature. A total of 119 patients with metastatic STS treated between June 2003 and December 2012 were analyzed for treatment outcome and prognostic factors. Median age was 37 years (range 2–72 years) with a male to female ratio of 1.5:1. Most common histologic subtypes were synovial sarcoma (36 %) and leiomyosarcoma (16 %). Median tumor size was 12 cm (range 1.6–30 cm). Twenty-four (20 %) patients were treated with multimodality therapy and 80 % patients received systemic chemotherapy alone. At a median follow-up of 10 months (range 1–66 months), the 2-year EFS and OS were 10 and 19 %, respectively, 
with a median EFS and OS of 6 and 10 months, respectively. Univariate analysis identified albumin ≤4 g/dl (p = 0.001), histologic subtypes other than synovial sarcoma (p = 0.02), non-extremity tumors (p = 0.03) and single modality treatment (p = 0.03) as factors predicting poor EFS; however, for OS, hemoglobin ≤10 g/dl (p = 0.02), tumor size >10 cm (p = 0.01) and single modality treatment (p = 0.04) were identified as poor prognostic factors. Multivariate analysis identified only serum albumin ≤4 g/dl (p = 0.002, HR 0.47, 95 % CI 0.29–0.75) associated with poor EFS; however, for OS, hemoglobin ≤10 g/dl (p = 0.009, HR 0.49, 95 % CI 0.29–0.83), tumor size >10 cm (p = 0.003, HR 2.11, 95 % CI 1.28–3.47) and single modality treatment (p = 0.01, HR 0.47, 95 % CI 0.25–0.86) emerged as poor prognostic factors. Serum albumin, tumor size, hemoglobin and treatment modality affect survival in metastatic STS.

Prognostic factors affecting survival in metastatic soft tissue sarcoma: an analysis of 110 patients.

Background Extragastrointestinal stromal tumors (EGISTs) are extremely rare mesenchymal tumors histologically and immunophenotypically similar to GI stromal tumors (GISTs). The aim of this study was to analyze the clinicopathological factors and treatment outcome in 13 patients with EGISTs treated at a tertiary care center. Methods Of 109 patients with GISTs treated at our center between April 2002 and December 2012, 13 patients with EGISTs were analyzed for clinicopathological factors and treatment outcome. Results Mean age was 45.8 (range 30-61) years, and females constituted 62% with a male:female ratio of 0.6:1. The most common tumor sites were mesentery in 10 patients and retroperitoneum in 3 patients. Mean tumor size was 11.7 (range 5-18) cm. Four (31%) patients were metastatic at presentation, the most common site of metastases being the liver in 3 (75%) patients. Lymph node enlargement was seen in 2 patients. Surgery was performed in 8 (62%) patients, 7 with localized disease, and 1 with metastatic disease. R0 resection was achieved in 3 (38%) patients. Five (71%) patients were considered as high-risk. Recurrences were seen in 3 patients (patient 3, 5 and 13) with localized disease after surgical resection, at 18, 7 and 137 months, respectively. At the last follow up, 7 patients were alive and 6 died of disease progression. The median overall survival was 34 (7-148) months. Conclusions EGISTs present at a younger age in the developing than in the developed countries. Females are more commonly affected than males. Lymph node metastases may be commonly present. Keywords Extrgastrointestinal stromal tumors, mesentery, retroperitoneum Ann Gastroenterol 2015; 28 (1): 105-108

Clinicopathological and treatment analysis of 13 extragastrointestinal stromal tumors of mesentery and retroperitoneum.

We evaluated long-term outcome of patients achieving complete response (CR) after autologous stem cell transplantation (ASCT) for multiple myeloma. Between April 1990 and June 2012 191 patients underwent ASCT. The median age was 53 years (range, 26–68 years), 135 were men. Pretransplant, patients received induction therapy with VAD (vincristine, doxorubicin, dexamethasone; n = 77), novel agents (n = 92), or alkylating agent-based, n = 22); 43% received more than one line of induction regimen. Response to transplant was defined as per EBMT criteria. The median follow-up for the entire group was 85 months (range, 6–232.5 months). Following transplant 109 (57.1%) patients achieved CR. Median progression-free survival (PFS) for patients with CR was higher compared to those with VGPR and PR, (107 vs. 18 vs. 18 months, P   7.1 G/dL at diagnosis (HR 4.756, P < 0.01) were associated with superior outcome. On landmark analysis at 12 months, PFS and OS continued to remain superior for patients attaining CR. Achievement of CR post transplant is associated with longer OS and PFS. Among complete responders, those who receive one line of induction therapy pretransplant have superior outcome.

Nida Iqbal

Papers

Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications

Imatinib: A Breakthrough of Targeted Therapy in Cancer

Prognostic factors affecting survival in metastatic soft tissue sarcoma: an analysis of 110 patients.

Clinicopathological and treatment analysis of 13 extragastrointestinal stromal tumors of mesentery and retroperitoneum.

Complete response after autologous stem cell transplant in multiple myeloma.