Cell density couples tissue mechanics to control the elongation speed of the body axis.

The vertebrate body forms by the addition of new tissues at the posterior end. This elongates the body axis, allowing continued anterior segmentation to produce the stereotypic body plan. This balance requires the elongation speed to be constrained.

Amino acid variants of SARS-CoV-2 papain-like protease have impact on drug binding.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused both a health and economic crisis around the world. Its papain-like protease (PLpro) is one of the protein targets utilized in designing new drugs that would aid vaccines in the fight against the virus. Although there are already several potential candidates for a good inhibitor of this protein, the degree of variability of the protein itself is not taken into account.

DYRK1A Kinase Inhibitors Promote β-Cell Survival and Insulin Homeostasis.

The rising prevalence of diabetes is threatening global health. It is known not only for the occurrence of severe complications but also for the SARS-Cov-2 pandemic, which shows that it exacerbates susceptibility to infections. Current therapies focus on artificially maintaining insulin homeostasis, and a durable cure has not yet been achieved.

Use of amantadine in the evaluation of response to chemotherapy in lung cancer: a pilot study.

Aim: The assessment of tumor response to therapy is of critical importance as it permits for a prospective end point evaluation and provides a guide to clinicians for making future treatment decisions. However, current practices in early evaluation of chemotherapy are insufficient. Amantadine is a substrate for .

Synthesis of new 4-butyl-arylpiperazine-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives and evaluation for their 5-HT and D receptor affinity and serotonin transporter inhibition.

A series of novel 4-butyl-arylpiperazine-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives were synthesized and evaluated for their 5-HT/D receptor affinity and serotonin reuptake inhibition. The compounds exhibited high affinity for the 5-HT receptor, (especially 4dK = 0.4 nM) which depended on the substitution pattern at the phenylpiperazine moiety.

Predictive value and clinical significance of increased SSAT-1 activity in healthy adults.

Aim: Spermidine/spermine N-acetyltransferase (SSAT-1) regulates cell growth, proliferation and death. Amantadine is converted by SSAT-1 to acetylamantadine (AA). In our earlier studies, although SSAT-1 was activated in patients with cancer, a number of ostensibly healthy adult volunteers had higher than expected AA concentration.

Use of amantadine as substrate for SSAT-1 activity as a reliable clinical diagnostic assay for breast and lung cancer.

Aim: Spermidine/spermine N-acetyltransferase (SSAT-1) plays a critical role in cell growth, proliferation and death, and is known to be activated in human cancer cells. Amantadine, a US FDA-approved antiviral drug, is a substrate for SSAT-1 and can be used to indirectly measure SSAT-1 activity because of its conversion to acetylamantadine (AA). This study was undertaken to further validate SSAT-1 activity in breast and lung cancer patients.

A Phase II Study of PF-03446962 in Patients with Advanced Malignant Pleural Mesothelioma. CCTG Trial IND.207.

There is no approved second-line systemic therapy option for malignant pleural mesothelioma (MPM), but targeting angiogenesis is an area of investigation. PF-03446962 is a fully human antibody against activin receptor-like kinase 1, which is commonly expressed in tumor vasculature. We performed a multicenter, open label, single-arm, two-stage phase II study of PF-03446962 in patients with MPM and progressive disease after platinum-based chemotherapy.

Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial.

Purpose: To present an updated survival analysis of an open-label, parallel-group, phase IIB trial of BLP25 liposome vaccine (L-BLP25) in patients with stage IIIB or IV non-small-cell lung cancer (NSCLC).

Methods: Patients were randomized to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received subcutaneous vaccinations of L-BLP25 930 μg weekly for 8 weeks, followed by maintenance vaccinations at 6-week intervals.

Cardiac function in survivors of acute lymphoblastic leukaemia and Hodgkin's lymphoma.

Aim: The study objective was to assess plasma N-terminal-pro-brain natriuretic peptide (BNP) levels and to evaluate left ventricular mass as well as left ventricular systolic and diastolic functions in 44 children who had undergone treatment for acute lymphoblastic leukaemia and Hodgkin's lymphoma, with regard to gender, age at disease onset, time that had passed since therapy completion, cumulative dose of antracyclines and mediastinal radiotherapy applied.

Methods: The median levels of pro-BNP were found to be higher in the whole study group as compared with the control (55.9 ± 53.

A multicenter open-label study to assess the safety of a new formulation of BLP25 liposome vaccine in patients with unresectable stage III non-small-cell lung cancer.

Introduction: BLP25 liposome vaccine (L-BLP25) is an innovative therapeutic cancer vaccine designed to induce an immune response resulting in elimination of tumor cells expressing the MUC1 antigen, which is overexpressed in non-small-cell lung cancer (NSCLC). Manufacturing modifications have produced subtle changes to the lipid A acyl chain composition of L-BLP25. This open-label phase II study was conducted to evaluate the safety of the new formulation in patients with unresectable stage IIIA/IIIB NSCLC.

A phase 2 study of platinum and gemcitabine in patients with advanced salivary gland cancer: a trial of the NCIC Clinical Trials Group.

Background: Salivary gland cancers are rare, histologically diverse, and varied in their biologic behavior and responsiveness to systemic therapy. To the authors' knowledge, there currently is no standard chemotherapy for these tumors, but cisplatin-based regimens are often used. This phase 2 trial evaluated the combination of gemcitabine with cisplatin (carboplatin in those with protocol-defined contraindications to cisplatin).

Inhibition of colon carcinogenesis by post-initiation induction of NQO1 in Sprague-Dawley rats.

Inducers of phase II detoxifying enzymes have been studied as chemopreventive agents for a variety of cancers. Phase II detoxifying enzymes may play a significant role in preventing carcinogen-induced colon cancer at the initiation and post-initiation stage, but the contribution of NAD(P) H:quinone oxidoreductase 1 (NQO1) to this effect remains unclear. Using the carcinogen-induced colon cancer Sprague-Dawley rat model, we previously showed that oltipraz selectively induces NQO1 in the colons of these rats without inducing other phase II detoxifying enzymes.

Impact of pretreatment factors on adverse events: a pooled analysis of North Central Cancer Treatment Group advanced stage non-small cell lung cancer trials.

Introduction: This pooled analysis was performed to examine the impact of pretreatment factors on severe (grade 3 or higher) adverse events (AE) in patients with advanced stage non-small cell lung cancer (NSCLC).

Methods: A pooled data set of 1053 participants from nine North Central Cancer Treatment Group clinical trials was used. Age, gender, performance status, tumor stage, body mass index, serum creatinine levels, hemoglobin levels, white blood cell counts, and platelet counts were evaluated univariately and multivariately using logistic regression.

A NAD(P)H:quinone oxidoreductase 1 polymorphism is a risk factor for human colon cancer.

Colon cancer is one of the most common cancers in North America and generally develops from colonic epithelial cells following initiation by carcinogens. We have shown that the phase II detoxifying enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1) contributes to the inhibition of carcinogen-induced colon cancer in rats at both the initiation and postinitiation stages. An inactivating polymorphism at base 609 of the NQO1 gene, (609)C (NQO1 *1) --> (609)T (NQO1 *2), occurs at high frequency in the human population.

A prognostic model for advanced stage nonsmall cell lung cancer. Pooled analysis of North Central Cancer Treatment Group trials.

Background: A pooled analysis was performed to examine the impact of pretreatment factors on overall survival (OS) and time to progression (TTP) in patients with advanced-stage nonsmall cell lung cancer (NSCLC) and to construct a prediction equation for OS using pretreatment factors.

Methods: A pooled data set of 1053 patients from 9 North Central Cancer Treatment Group trials was used. Age, gender, Eastern Cooperative Oncology Group performance status (PS), tumor stage (Stage IIIB vs.

Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer.

Purpose: To evaluate the effect of BLP25 liposome vaccine (L-BLP25) on survival and toxicity in patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Secondary objectives included health-related quality of life (QOL) and immune responses elicited by L-BLP25.

Patients And Methods: Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and stable or responding stage IIIB or IV NSCLC after any first-line chemotherapy were prestratified by stage and randomly assigned to either L-BLP25 plus best supportive care (BSC) or BSC alone.

Randomized phase III study of fludarabine phosphate versus cyclophosphamide, vincristine, and prednisone in patients with recurrent low-grade non-Hodgkin's lymphoma previously treated with an alkylating agent or alkylator-containing regimen.

Purpose: To compare in a phase III study the safety and efficacy of fludarabine to that of cyclophosphamide, vincristine, and prednisone (CVP) in recurrent, low-grade, non-Hodgkin's lymphoma after previous response to systemic treatment.

Patients And Methods: Patients were randomized to fludarabine (25 mg/m(2) intravenously on days 1 to 5, every 28 days) or CVP (cyclophosphamide 750 mg/m(2) and vincristine 1.2 mg/m(2) both intravenously on day 1 and prednisone 40 mg/m(2) orally on days 1 to 5, every 21 days).

Phase II study of sequential topotecan and etoposide in patients with intermediate grade non-Hodgkin's lymphoma: a National Cancer Institute of Canada Clinical Trials Group study.

Preliminary results indicate that inhibitors of the nuclear enzyme topoisomerase (topo) I, such as topotecan, may be active in non-Hodgkin's lymphoma (NHL). Pre-clinical studies have shown sequential administration of a topo I and II inhibitor has supra-additive anti-tumor effects in some model systems, and that greater cytotoxicity occurs if the topo I inhibitor is given first. We enrolled, 22 eligible patients with relapsed or refractory intermediate grade NHL in a phase II study ofsequential administration of topotecan 1.

Significance of neuron-specific enolase levels before and during therapy for small cell lung cancer.

The level of serum neuron-specific enolase (NSE) has been implicated as a prognostic factor for patients with small cell lung cancer (SCLC). A prospective evaluation was undertaken to assess the prognostic significance of pretreatment NSE and treatment-induced minimum NSE values in patients with SCLC. Patients from two Phase III North Central Cancer Treatment Group trials [one for patients with extensive stage SCLC and one for patients with limited stage SCLC] were asked to enter this laboratory correlational trial.

Distinct B-cell clonal bands in Helicobacter pylori gastritis with lymphoid hyperplasia.

Helicobacter pylori (Hp)-associated gastritis is a risk factor for gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Clonal B-cell populations are present in both reactive and neoplastic MALT tissue, thus limiting their usefulness in the evaluation of gastric lymphoid infiltrates in endoscopic biopsy specimens. The aim of this study was to identify the presence of clonal B-cell populations in Hp-gastritis with MALT and to assess their usefulness in distinguishing reactive from malignant infiltrates.