NRAMP family in plants: Contribution to cadmium accumulation.

The Natural Resistance Associated Macrophage Proteins (NRAMPs) are membrane-targeted transporters with low substrate specificity, that mediate the import (translocation to the cytoplasm) of metals, mainly essential nutrients, e.g. iron (Fe), manganese (Mn), zinc (Zn), cobalt (Co), copper (Cu) or nickel (Ni).

Efficacy of radiotherapy and radiotherapy with hyperthermia to delay change of systemic therapy in patients with metastatic melanoma.

Background: The use of radiotherapy (RT) and RT with hyperthermia (HT) as a local treatment for oligoprogression in many tumors is becoming increasingly prevalent. However, there is currently limited data regarding RT efficacy in prolonging systemic therapy in melanoma. To address this lack of evidence, we conducted a single-institution study to establish the role of RT and RT + HT in delaying the time to systemic treatment switch in metastatic melanoma (MM).

Chemotherapy efficacy in advanced melanoma patients after failure of immune checkpoint and BRAF/MEK inhibitors.

Introduction: Despite the introduction of new therapies for the treatment of advanced melanoma, treatment is ineffective for a certain number of patients. The efficacy of chemotherapy after failure of anti-programmed death receptor (PD-1) immunotherapy alone or combined with anti-cytotoxic T-lymphocyte-associated antigen (CTLA) is not fully understood. It is believed that due to the immunomodulatory effect of cytostatic agents, its efficacy may be greater when applied after the failure of immunotherapy.

Discontinuation of Immune Checkpoint Inhibition in Patients with Advanced Unresectable Melanoma Achieving CR, PR, or SD.

Background: The optimal duration of immunotherapy (ITH) remains undefined for patients with metastatic melanoma, and debates on de-escalation strategies are ongoing. Patients in the pivotal KEYNOTE and CheckMate trials who experienced a complete response (CR) on ITH had long-term responses, even after treatment was terminated early because of toxicity or at the physician's discretion.

Objective: Our study explores the duration of planned ITH drug holidays-intentional ITH suspension until disease progression off treatment-in patients with unresectable and metastatic melanoma treated for at least 6 months with ITH.

Avelumab plus axitinib in patients with advanced gastrointestinal stromal tumor.

Background: Treatment options for patients with advanced gastrointestinal stromal tumor (GIST) after failure of standard therapies with tyrosine kinase inhibitor (TKI) remain very limited. As vascular endothelial growth factor (VEGF) inhibitors are considered to have immunomodulatory effects, we hypothesized that the combination of VEGF and PD-L1 inhibitors may have a synergistic effect and enhance the efficacy of both therapies.

Methods: AXAGIST was a phase II trial evaluating the efficacy and safety of avelumab 10 mg/kg iv Q2W in combination with axitinib 5 mg po BID in patients with unresectable/metastatic GIST after failure of standard therapy.

The Role of Ferulic Acid in Selected Malignant Neoplasms.

Ferulic acid (FA) is a polyphenol that is found in plants and fruits. It has a wide range of anticancer properties, including participating in cell apoptosis, inhibiting invasion and angiogenesis, and acting synergistically with standard cytostatic agents in malignant tumors. A range of molecular mechanisms are involved in anticancer activity and include the following ones: activation of cell-cycle-related proteins and enzymes such as p53, p21, Bax, and pro-caspases 3 and 9, reduction of cyclin D1 and E, proapoptotic Bcl-2, MMP-9, and NF-kV, which decrease VEGF, leading to cell cycle arrest at G0/G1 phase and death of cancer cells.

Systemic inflammation index is a predictive and prognostic factor in patients with liposarcoma or leiomyosarcoma treated with trabectedin.

Trabectedin is a chemotherapeutic agent that has shown activity in the treatment of patients with soft tissue sarcomas after failure of anthracycline-based therapy and the best results were recorded in the treatment of L-sarcomas. There is a need for prognostic and predictive factors that will help clinicians with therapy selection. In this study we aim to analyze treatment results, prognostic and predictive factors in patients treated with trabectedin in routine clinical practice.

Epithelioid inflammatory myofibroblastic sarcoma with exceptionally long response to lorlatinib-a case report.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare and aggressive subtype of inflammatory myofibroblastic tumor. The disease is associated with rearrangements of the anaplastic lymphoma kinase (ALK). In this paper, we present the clinicopathological features and treatment of a female patient diagnosed with EIMS.

Misdiagnosis Based on Neoplastic Markers-Extremely High Alpha-Fetoprotein in Patients with Intrahepatic Cholangiocarcinoma with Literature Review of the Published Cases.

: Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are two tumor markers that are widely used in the differential diagnosis in patients with primary liver tumors. Very high levels of AFP are sporadically observed in patients with intrahepatic cholangiocarcinoma (ICC) and may cause an incorrect initial diagnosis of hepatocellular carcinoma (HCC). : Two cases of tumors in cirrhotic livers were described, in which the initial diagnosis, based on very high AFP levels (Patient I: 10,464 ng/mL, Patient II: 2212 ng/mL, reference range: ≤8.

Long-term efficacy of neoadjuvant-adjuvant targeted therapy in borderline resectable stage IIIB-D and IV melanoma.

Background: Neoadjuvant-adjuvant therapy for locally advanced or potentially resectable metastatic melanoma was expected to improve operability and clinical outcomes over upfront surgery and adjuvant treatment only.

Methods: Forty-seven consecutive patients were treated with neoadjuvant-adjuvant BRAF inhibitors (BRAFi)/MEK inhibitors (MEKi) and surgery.

Results: Twelve (26%) patients achieved a pathological complete response and 10 (21%) patients achieved a near-complete response.

Preoperative-postoperative immunotherapy as treatment of borderline resectable and oligoprogressive stage III B-D and IV melanoma.

Introduction: Perioperative therapy has gained significant importance in patients with advanced melanoma. Currently, there is little data on the routine use of preoperative immunotherapy in metastatic melanoma outside clinical trials. This study aimed to evaluate the effectiveness of preoperative treatment in patients with borderline resectable stage III or IV melanoma as well as in oligoprogressing stage IV cases; the secondary aim is to describe the safety of surgery after immunotherapy.

Silver Shell Thickness-Dependent Conductivity of Coatings Based on Ni@Ag Core@shell Nanoparticles.

Introductions: Ink based on metallic nanoparticles has been widely used so far for the fabrication of electronic circuits and devices using printing technology. This study aimed at the analysis of the effect of the silver shell thickness of nickel@silver core@shell (Ni@Ag) nanoparticles (NPs) on the fabrication and conductive properties of deposited coatings.

Methods: The process of the synthesis of Ni@Ag NPs with various silver shell thicknesses was developed.

Hedgehog pathway in sarcoma: from preclinical mechanism to clinical application.

Sarcomas are a diverse group of malignant neoplasms of mesenchymal origin. They develop rarely, but due to poor prognosis, they are a challenging and significant clinical problem. Currently, available therapeutic options have very limited activity.

Tobacco as an efficient metal accumulator.

Tobacco (Nicotiana tabacum L.) is an important industrial crop plant. However, it efficiently accumulates metals, primarily cadmium (Cd) and also zinc (Zn), in its leaves.

In search of effective therapies: the current landscape of phase II trials in patients with advanced soft tissue sarcoma.

Purpose: Soft tissue sarcomas (STS) are diagnosed in 4-6 cases per 100 000 people a year and are associated with an unfavorable prognosis. Around one-third of patients will develop metastatic disease that requires palliative systemic therapy. Current therapeutic options have limited activity, and new treatments are tested, mainly in phase II trials.

Regulation and Function of Metal Uptake Transporter NtNRAMP3 in Tobacco.

Natural resistance-associated macrophage protein () genes encode proteins with low substrate specificity, important for maintaining metal cross homeostasis in the cell. The role of these proteins in tobacco, an important crop plant with wide application in the tobacco industry as well as in phytoremediation of metal-contaminated soils, remains unknown. Here, we identified NtNRAMP3, the closest homologue to NRAMP3 proteins from other plant species, and functionally characterized it.

Long Term Results and Prognostic Biomarkers for Anti-PD1 Immunotherapy Used after BRAFi/MEKi Combination in Advanced Cutaneous Melanoma Patients.

(1) Background: BRAFi/MEKi are usually offered as a first line treatment for patients requiring rapid response; with elevated lactate dehydrogenase (LDH) activity, large tumor burden, and with brain metastases. The efficacy of second line therapies after BRAFi/MEKI failure is now well defined. (2) Methods: Patients treated with first line target BRAFi/MEKi therapy (vemurafenib plus cobimetinib, dabrafenib plus trametinib or encorafenib plus binimetinib); and for the second line treatment immunotherapy with programmed cell death 1 (PD-1) checkpoint inhibitors (nivolumab or pembrolizumab) with at least one cycle of second line were analyzed for survival and prognostic biomarkers.

The Use of ctDNA for Mutation Testing in Routine Clinical Practice in Patients with Advanced Melanoma.

Assessment of mutation status is mandatory in advanced, treatment-naïve melanoma patients. Liquid biopsy can be an alternative in cases with inadequate or unavailable tumor tissue. The aim of our study was to evaluate the clinical utility of plasma circulating tumor DNA analysis for mutation testing and to assess outcomes of therapy with BRAF/MEK inhibitors initiated based on the liquid biopsy results.

Efficacy of immunotherapy beyond RECIST progression in advanced melanoma: a real-world evidence.

Immunotherapy (ITH) holds the possibility of tumor burden decrease after initial RECIST 1.1 defined progression. The clinical concept of treating selected patients (pts) beyond disease progression (PD) is supported by so-called pseudoprogression phenomenon.

Treatment of Locally Advanced Merkel Cell Carcinoma-A Multi-Center Study.

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a high risk of recurrence and poor prognosis. The treatment of locally advanced disease involves surgery and radiotherapy. To analyze real-life treatment patterns and clinical outcomes, we conducted a retrospective analysis of data from 161 MCC patients treated with curative intent in four oncological centers in Poland.

Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF Mutation-Positive Melanoma.

Neoadjuvant therapy for locally advanced disease or potentially resectable metastatic melanoma is expected to improve operability and clinical outcomes over upfront surgery and adjuvant treatment as it is for sarcoma, breast, rectal, esophageal, or gastric cancers. Patients with locoregional recurrence after initial surgery and those with advanced regional lymphatic metastases are at a high risk of relapse and melanoma-related death. There is an unmet clinical need to improve the outcomes for such patients.

Age as a Prognostic Factor in Patients with Ewing Sarcoma-The Polish Sarcoma Group Experience.

Ewing sarcoma (ES) is a rare and aggressive disease that requires multidisciplinary treatment with the use of chemotherapy, radiotherapy, and surgery. Our retrospective study aimed to analyze the prognostic factors and treatment results in different age groups of patients. Between 1998 and 2018, 569 patients with ES were treated in two referral centers.

Lyme Neuroborreliosis in Children.

Lyme neuroborreliosis (LNB) is an infectious disease, developing after a tick bite and the dissemination of spirochetes reach the nervous system. The infection occurs in children and adults but with different clinical courses. Adults complain of radicular pain and paresis, while among the pediatric population, the most common manifestations of LNB are facial nerve palsy and/or subacute meningitis.