CUTANEOUS SQUAMOUS CELL CARCINOMA- A CASE REPORT

Cutaneous squamous cell carcinoma (cSCC) is a malignant neoplasm of the skin characterized by an aberrant 1 proliferation of keratinocytes. The usual presentation of skin malignancies include ulceration, growth, a change in mole, unusual form or bleeding due to various etiological factors. There exists a diagnostic challenge, as many benign conditions present similarly, thereby altering the treatment strategy. 2 Although Cutaneous Squamous Cell Carcinoma usually display a benign clinical behaviour, it can be both locally invasive and metastatic Here we report a case of an elderly female who presented with a proliferative growth in right forearm for the past 1 year, from a pre-existing mole, which on examination had features of all the three cutaneous malignancies resulting in a diagnostic uncertainty and which on further workup was diagnosed as a well differentiated squamous cell carcinoma

Molecular Pathogenesis of Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin with two distinct etiologies. Clonal integration of Merkel cell polyomavirus DNA into the tumor genome with persistent expression of viral T antigens causes at least 60% of all MCC. UV damage leading to highly mutated genomes causes a nonviral form of MCC. Despite these distinct etiologies, both forms of MCC are similar in presentation, prognosis, and response to therapy. At least three oncogenic transcriptional programs feature prominently in both forms of MCC driven by the virus or by mutation. Both forms of MCC have a high proliferative growth rate with increased levels of cell cycle–dependent genes due to inactivation of the tumor suppressors RB and p53, a strong MYC signature due to MYCL activation by the virus or gene amplification, and an attenuated neuroendocrine differentiation program driven by the ATOH1 transcription factor. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 16 is January 25, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Plant homeodomain proteins provide a mechanism for how leaves grow wide

ABSTRACTThe mechanisms whereby leaf anlagen undergo proliferative growth and expansion to form wide, flat leaves are unclear. The maize gene NARROWSHEATH1 (NS1) is a WUSCHEL-related homeobox3 (WOX3) homolog expressed at the margins of leaf primordia, and is required for mediolateral outgrowth. To investigate the mechanisms of NS1 function, we used chromatin immunoprecipitation and laser-microdissection RNA-seq of leaf primordial margins to identify gene targets bound and modulated by NS1. Microscopic analyses of cell division and gene expression in expanding leaves, and reverse genetic analyses of homologous NS1 target genes in Arabidopsis, reveal that NS1 controls mediolateral outgrowth by repression of a growth inhibitor and promotion of cell division at primordial leaf margins. Intriguingly, homologous WOX gene products are expressed in stem cell-organizing centers and traffic to adjoining cells to activate stem-cell identity non-autonomously. In contrast, WOX3/NS1 does not traffic, and stimulates cell divisions in the same cells in which it is transcribed.

The phosphatase inhibitor LB-100 acts synergistically with the NPR2 agonist BMN-111 to improve bone growth

ABSTRACTActivating mutations in fibroblast growth factor receptor 3 (FGFR3) and inactivating mutations in the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase both result in decreased production of cyclic GMP (cGMP) in chondrocytes and severe short stature, causing achondroplasia (ACH) and acrosomelic dysplasia type Maroteaux, respectively. Previously we showed that an NPR2 agonist BMN-111 (vosoritide) increases bone growth in mice mimicking ACH (Fgfr3Y367C/+), and that in control growth plate chondrocytes, FGFR3 signaling decreases NPR2 activity by dephosphorylating the NPR2 protein. Here we tested whether a phosphatase inhibitor (LB-100) could enhance bone growth in ACH. In ex vivo imaging experiments using a FRET sensor to measure cGMP production in chondrocytes of living tibias from newborn mice, LB-100 counteracts the FGF-induced dephosphorylation and inactivation of NPR2. In ex vivo experiments with Fgfr3Y367C/+ mice, LB-100 in combination with BMN-111 increases the rate of femur growth by ∼25% vs BMN-111 alone, restores chondrocyte terminal differentiation, increases the proliferative growth plate area of the femur, and reduces the activity of the MAP kinase pathway. Our results provide a proof of concept that a phosphatase inhibitor could be used together with an NPR2 agonist to enhance cGMP production as a therapy for ACH.GRAPHICAL ABSTRACT

Development of an Organic–Inorganic Nanostructured Hybrid Dental Biocomposite

Dental pathologies such as caries is one of the most prevalent diseases worldwide. Dental pulp contains stem cells capable of regenerating the dentine in the tooth, consequently, healthy dental pulp is essential for long term tooth survival. The aim of this study was to incorporate a variety of polymers that provide strength, an antibacterial substance and a protein-based polymer to provide cell support. These components were combined into a triphasic hybrid dental biocomposite (3HB), that together could provide regenerative properties for the pulp tissue. The 3HB biocomposite was incorporated into Organic–inorganic nanostructured materials such as Mineral Trioxide Aggregate (MTA) as a base to assemble a hybrid dental biocomposite. The effects of the 3HB on cytotoxicity was examined in mouse dental pulp cells, MDPC-23. In vitro studies showed that 3HB supported the proliferative growth of the cells significantly more than the no treatment control. 3HB also caused little stress to the cells and supported cell viability. Fourier transform infrared (FTIR) spectra confirmed the presence of polymer functional groups within the 3HB biocomposite. Therefore, 3HB compound has the potential to be applied as a pulp wound dressing providing superior cytocompatibility than the present options but also may be indispensable for the regeneration of dental pulp.

Small Cell Neuroendocrine Carcinoma of Tonsil – A Rare Occurrence

Small cell neuroendocrine carcinomas of tonsil are extremely rare cancers and only a few cases have been reported till date. They carry a poor prognosis. Paraneoplastic syndromes like SIADH, Cushing’s syndrome and Eaton-Lambert myasthenic syndrome can be found associated with these carcinomas. The tumor can metastasize to liver, lungs, bone, brain and skin. A 70-year-old male presented with a 2-month history of pain in throat which was moderate to severe in intensity and intermittent. Local examination of oropharynx revealed a 5×5 cm ulcero-proliferative growth over the right tonsil extending to right side of base of tongue, vallecula, and right retromolar trigone. Multiple matted lymph nodes were palpable in the right cervical region. Histopathological examination of tissue sample from the growth over the right tonsil revealed small cell neuroendocrine carcinoma. On immunohistochemistry, chromogranin and CD56 were positive. Patient received 2-courses of neoadjuvant chemotherapy with cisplatin and etoposide. Then the patient was planned for external beam radiation therapy with dose of 60 Gy in 30 fractions in 6 weeks. Small cell neuroendocrine carcinoma of tonsil are likely to be very aggressive with a tendency of developing early regional lymphatic and systemic metastases. More research and clinical trials shall be explored to obtain a standard treatment strategy for these patients.

Ankhd1 enhances polycystic kidney disease development via promoting proliferation and fibrosis

ABSTRACTAutosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic kidney disorder resulting in 10% of patients with renal failure. The molecular events responsible for the relentless growth of cysts are not defined. Thus, identification of novel drivers of ADPKD may lead to new therapies. Ankyrin Repeat and Single KH domain-1 (ANKHD1) controls cancer cell proliferation, yet its role in ADPKD is unexplored. Here, we present the first data that identify ANKHD1 as a driver of proliferative growth in cellular and mouse models of ADPKD. Using the first Ankhd1-deficient mice, we demonstrate that Ankhd1 heterozygosity potently reduces cystic growth and fibrosis, in a genetically orthologous mouse model of ADPKD. We performed transcriptome-wide profiling of patient-derived ADPKD cells with and without ANKHD1 siRNA silencing, revealing a major role for ANKHD1 in the control of cell proliferation and matrix remodelling. We validated the role of ANKHD1 in enhancing proliferation in patient-derived cells. Mechanistically ANKHD1 promotes STAT5 signalling in ADPKD mice. Hence, ANKHD1 is a novel driver of ADPKD, and its inhibition may be of therapeutic benefit.

A rare case of duodenal cancer with achalasia cardia

Duodenal adenocarcinoma constitutes 0.4% of gastrointestinal malignancies. Achalasia incidence rate is 0.5-1.2 per 100000. The combination is rare. This is a report of a 68-year-old male from Nepal with history of five years abdominal pain, dysphasia and weight loss. Duodenoscopy could confirm ulcero-proliferative growth at D1-D2. Barium meal depicted features of achalasia cardia. No similar case report suggests that occurrence of duodenal carcinoma and achalasia cardia is merely co- incidental. Discussion: No similar case report suggests that occurrence of duodenal carcinoma and achalasia cardia is merely co- incidental. Consent: Informed consent was obtained from the patient for publication of this case report .