3-Formylchromone Counteracts STAT3 Signaling Pathway by Elevating SHP-2 Expression in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the leading cancers that contribute to a large number of deaths throughout the globe. The signal transducer and activator of transcription 3 (STAT3) is a tumorigenic protein that is overactivated in several human malignancies including HCC. In the present report, the effect of 3-formylchromone (3FC) on the STAT3 signaling pathway in the HCC model was investigated. 3FC downregulated the constitutive phosphorylation of STAT3 and non-receptor tyrosine kinases such as JAK1 and JAK2. It also suppressed the transportation of STAT3 to the nucleus and reduced its DNA-binding ability. Pervanadate treatment overrode the 3FC-triggered STAT3 inhibition, and the profiling of cellular phosphatase expression revealed an increase in SHP-2 levels upon 3FC treatment. The siRNA-driven deletion of SHP-2 led to reinstate STAT3 activation. 3FC downmodulated the levels of various oncogenic proteins and decreased CXCL12-driven cell migration and invasion. Interestingly, 3FC did not exhibit any substantial toxicity, whereas it significantly regressed tumor growth in an orthotopic HCC mouse model and abrogated lung metastasis. Overall, 3FC can function as a potent agent that can display antitumor activity by targeting STAT3 signaling in HCC models.

Effect of sub-acute and sub-chronic administration of Vicia faba's cooking medium containing EDTA on hepato-renal functions in albino mice

To decrease the Vicia faba beans cooking time, some chefs added ethylene diamine tetra-acetic acid (EDTA) during the cooking process. This study addressed the effect of sub-acute and chronic administrations of faba bean's cooking media containing EDTA (C.M./EDTA) on hepato-renal functions in mice. Ninety male mice were divided into three groups (n = 30). The group 1 (Gp1) divided into Gp1a and Gp1b, both were served as control for sub-acute and sub-chronic treatments. Gp2 divided into Gp2a and Gp2b then administered with 200 µl of C.M. for 15 and 90 days, respectively. Gp3 divided into Gp3a and Gp3b then administered 200 µl of C.M./EDTA (10 mg/kg) for 15 and 90 days, respectively. Hematological, biochemical, and histopathological alterations were investigated. The results showed that sub-acute administration of C.M./EDTA did not show any signs of toxicity, however, sub-chronic administration showed substantial toxicity evidenced by alterations in some biochemical and histological investigations.

Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma in the Era of New Drugs and CAR-T Cell Therapy

MCL is an uncommon lymphoproliferative disorder that has been regarded as incurable since its identification as a distinct entity. Allogeneic transplantation for two decades has represented the only option capable of ensuring prolonged remissions and possibly cure. Despite its efficacy, its application has been limited by feasibility limitations and substantial toxicity, particularly in elderly patients. Nevertheless, the experience accumulated over time has been wide though often scattered among retrospective and small prospective studies. In this review, we aimed at critically revise and discuss available evidence on allogeneic transplantation in MCL, trying to put available evidence into the 2020 perspective, characterized by unprecedented development of novel promising therapeutic agents and regimens.

Rapid, Fatal Acute Right Ventricular Failure After Locoregional Cytokine Therapy for Uveal Melanoma Liver Metastases

Locoregional cytokine treatment, or immunoembolization, is an experimental targeted therapy for uveal melanoma metastatic to the liver. Unlike systemic cytokine treatments that have been associated with substantial toxicity, this method of drug delivery appears to be better tolerated. Because this newer therapy is being prescribed more widely, oncologists, interventional radiologists, cardiologists, pulmonologists, critical care specialists, and other providers should become familiar with potential adverse reactions. We describe the case of a 67-year-old man who had metastatic uveal melanoma. Before he underwent liver-directed immunoembolization, he had elevated markers of endothelial dysfunction. He died after the rapid onset of acute right ventricular failure from severe pulmonary hypertension with possible superimposed isolated right ventricular takotsubo cardiomyopathy. In discussing this rare case, we focus on the differential diagnosis.

Incidence of chemotherapy-induced nausea and vomiting in 2008

e20660 Background: The authors determined the incidence of acute and delayed chemotherapy-induced nausea and vomiting (CINV) among new patients (pts) receiving chemotherapy with modern antiemetic prophylaxis in 2008. Methods: A prospective observational study of adult cancer pts receiving, for the first time, moderately or highly emetogenic chemotherapy (MEC or HEC) was performed. Study participants were called on day 2 and day 8, after first and second cycle, to evaluate acute and delayed emesis according a 10-item questionnaire. All patients received, before and after their chemotherapy, the optimal antiemetic prophylaxis according to the 2006 Update of ASCO Guideline for Antiemetics. Results: 131 consecutive pts were enrolled between January and June 2008. At cycle 1, on 124 assessable pts for acute emesis: 68 pts received MEC and 18, HEC. 5.6% developed acute vomiting (5.9% for MEC and 5.6% for HEC) and 33.1%, acute nausea (39.7% for MEC and 44.4% for HEC). At cycle 1, on 101 assessable pts for delayed emesis: 5% experienced delayed vomiting (5.1% for MEC and 6.3% for HEC) and 17.8%, delayed nausea (18.6% for MEC and 31.3% for HEC). At cycle 2, on 121 assessable pts for acute emesis: 62 pts received MEC and 18, HEC. 8.3% developed acute vomiting (6.5% for MEC and 16.3% for HEC) and 31.4%, acute nausea (35.5% for MEC and 44.4% for HEC). At cycle 2, on 96 assessable pts for delayed emesis: 5.2% experienced delayed vomiting (3.3% for MEC and 9.1% for HEC) and 19.8%, delayed nausea (23% for MEC and 27.3% for HEC). Conclusions: Though the application of the last antiemetic recommendations, CINV, especially nausea, remained a substantial toxicity for patients receiving chemotherapy, pointing out the need for improved therapeutic intervention. [Table: see text]

Phase II Trial of Doxorubicin Plus Escalated High-Dose Ifosfamide in Patients With Advanced Soft Tissue Sarcomas of the Adult: A Study of the Spanish Group for Research on Sarcomas (GEIS)

Background.To explore the tolerance and the activity of high-dose ifosfamide (IFOS) combined with doxorubicin (DXR) at 50 mg/m2every 4 weeks in patients with soft tissue sarcomas.Methods.DXR was given IV bolus and IFOS by continuous infusion at 2 g/m2/day. Initial IFOS dose (12 g/m2) was adjusted to 10, 13, or 14 g/m2according to toxicity.Results.Seventy patients received 277 cycles (median 3 cycles, range 1–10), 34% with IFOS dose increased, 30% decreased, and 48% delivered at 12 g/m2. Toxicity grade 4 occurred on granulocytes (67% of patients) or platelets (19%), 54% had febrile neutropenia, 31% grade 3/4 asthenia, and 26% abandoned the study due to toxicity. Three toxic deaths occurred. In 57 non-GIST patients objective activity was 45.6% (95% CI, 32 to 58%).Conclusion.At least 4 cycles were tolerated by 71% of patients, most receiving DXR 50 mg/m2plus IFOS 10–12 g/m2, with substantial toxicity.

Antithymocyte globulin has limited efficacy and substantial toxicity in unselected anemic patients with myelodysplastic syndrome

Antithymocyte globulin (ATG) has recently been popularized as an effective treatment in myelodysplastic syndrome (MDS). We treated 8 anemic MDS patients (refractory anemia [RA] and refractory anemia with excess blasts [RAEB-1]) with ATG (40 mg/kg/d for 4 days) and prednisone in a phase 2 trial. The study was stopped early according to a preset termination rule because of lack of efficacy. There were no salutary responses. Toxicities included serum sickness (in all patients), transient neutropenia and thrombocytopenia, diarrhea, vomiting, and syncope with a generalized seizure. At least 3 patients had the HLA-DR15 (DR2) allele. We conclude that the risk-benefit ratio of ATG in an unselected population of MDS patients may be unfavorable, and more work is needed to define the subset of patients who will respond to ATG before its widespread use can be recommended.

Mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) chemotherapy for gynecological sarcomas

This report summarizes our experience with the combination of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) for patients with gynecological sarcomas. We reviewed the records of all patients who had received the MAID regimen for a gynecological sarcoma between 1993 and 2000. The MAID regimen was administered intravenously every 4 weeks in the hospital as follows: (1) mesna 1500 mg/m2/day × 4 days; (2) doxorubicin 15 mg/m2/day × 3 days; (3) ifosfamide 1500 mg/m2/day × 3 days; (4) dacarbazine 250 mg/m2/day × 3 days. The results of treatment with MAID were disappointing. Overall, the response rate was 9% with one complete response and one partial response (both in patients with uterine leiomyosarcoma). We did not observe any responses among the patients with carcinosarcomas of either ovarian or uterine origin. The median progression-free interval and survival were 11 months and 29 months, respectively. This regimen was associated with substantial toxicity (including a death from neutropenic sepsis) as well as high cost and inconvenience due to the requirement for inpatient administration. Although our study contains a limited number of patients with a variety of gynecological sarcomas, our review has led us to discontinue using MAID. It remains to be established if any combination chemotherapy regimen is better than single agent treatment.

Allogeneic marrow transplantation for refractory Hodgkin's disease.

Eight patients with refractory Hodgkin's disease received intensive combination chemotherapy conditioning with cyclophosphamide, carmustine (BCNU), and etoposide (VP 16-213), and allogeneic marrow transplants. All patients achieved complete responses. Three patients relapsed; two died of Hodgkin's disease and one of chronic graft-v-host disease (GVHD) and infection. In all, four patients died due to transplant-related toxicity. One patient developed a fatal B-cell lymphoproliferative disorder soon after transplantation, and died without evidence of Hodgkin's disease. One patient is alive and free of progression 29 months after transplantation. These data indicate that allogeneic marrow transplantation may be considered as therapy for selected patients with advanced Hodgkin's disease and, despite substantial toxicity, will occasionally result in long-term responses. Better patient selection would likely improve results.