- The Route to 'Chemobrain' - Computational probing of neuronal LTP pathway. [Journal Article]
- SRSci Rep 2019 Jul 03; 9(1):9630
- Chemotherapy causes deleterious side effects during the course of cancer management. The toxic effects may be extended to CNS chronically resulting in altered cognitive function like learning and mem…
Chemotherapy causes deleterious side effects during the course of cancer management. The toxic effects may be extended to CNS chronically resulting in altered cognitive function like learning and memory. The present study follows a computational assessment of 64 chemotherapeutic drugs for their off-target interactions against the major proteins involved in neuronal long term potentiation pathway. The cancer chemo-drugs were subjected to induced fit docking followed by scoring alignment and drug-targets interaction analysis. The results were further probed by electrostatic potential computation and ligand binding affinity prediction of the top complexes. The study identified novel off-target interactions by Dactinomycin, Temsirolimus, and Everolimus against NMDA, AMPA, PKA and ERK2, while Irinotecan, Bromocriptine and Dasatinib were top interacting drugs for CaMKII. This study presents with basic foundational knowledge regarding potential chemotherapeutic interference in LTP pathway which may modulate neurotransmission and synaptic plasticity in patient receiving these chemotherapies.
- Leptomeningeal spread of gestational trophoblastic neoplasia in a 19-year old woman. [Case Reports]
- GOGynecol Oncol Rep 2019; 29:29-33
- Gestational trophoblastic neoplasia (GTN) with brain metastasis is usually seen in patients with advanced disease. Ten percent of metastatic gestational trophoblastic disease involves the brain and s…
Gestational trophoblastic neoplasia (GTN) with brain metastasis is usually seen in patients with advanced disease. Ten percent of metastatic gestational trophoblastic disease involves the brain and spinal cord, most often manifesting as an intracerebral mass or subdural hematoma, and are generally known to be a poor prognostic factor (Dadlani et al., 2010). Leptomeningeal metastases are tremendously rare and not well documented in the literature. A standardized treatment regimen for patients with brain metastases has not been established and is controversial due to a number of multimodal treatments that have been published in the literature without a prospective trial having been completed. We report a case of a patient with gestational trophoblastic disease that metastasized to the lung and leptomeninges, who after treatment with induction chemotherapy using etoposide (E) and cisplatin (P) followed by etoposide, methotrexate and dactinomycin (EMA) chemotherapy achieved a complete response without brain radiation (Han et al., 2012).
- Increased local failure for patients with intermediate-risk rhabdomyosarcoma on ARST0531: A report from the Children's Oncology Group. [Journal Article]
- CCancer 2019 Jun 07
- CONCLUSIONS: Despite interventions designed to enhance local control, local control was inferior on ARST0531 in comparison with D9803. The reason for this is unclear, but it could be the reduced cyclophosphamide dose on ARST0531.
- Chemotherapy for gestational trophoblastic neoplasia patients with a FIGO score of 12 or greater: A multistudy analysis. [Journal Article]
- EJEur J Obstet Gynecol Reprod Biol 2019; 238:164-169
- CONCLUSIONS: EMA/CO, EP/EMA, and FAEV yielded comparable CR rates in GTN patients with a FIGO score ≥12 in the first-line setting.
- Long-term remission of bilateral Wilms tumors that developed from premature separation of chromatids/mosaic variegated aneuploidy syndrome due to bilateral nephrectomy and peritoneal dialysis. [Journal Article]
- PBPediatr Blood Cancer 2019; 66(8):e27804
- We report a 38-month-old Japanese male with premature chromatid separation/mosaic variegated aneuploidy syndrome bearing biallelic BUB1B germline mutations who suffered from bilateral Wilms tumor. Af…
We report a 38-month-old Japanese male with premature chromatid separation/mosaic variegated aneuploidy syndrome bearing biallelic BUB1B germline mutations who suffered from bilateral Wilms tumor. After right nephrectomy, dactinomycin monotherapy was administered for the left Wilms tumor; however, severe adverse reaction prevented the patient from receiving further chemotherapy. Left nephrectomy was then performed without postoperative chemotherapy. The patient survived for 15 months after bilateral nephrectomy without peritoneal relapse, metastasis of Wilms tumor, or the occurrence of rhabdomyosarcoma and maintained a good quality of life while receiving peritoneal dialysis at home.
- ABCB1 (C1236T) Polymorphism Affects P-Glycoprotein-Mediated Transport of Methotrexate, Doxorubicin, Actinomycin D, and Etoposide. [Journal Article]
- DCDNA Cell Biol 2019; 38(5):485-490
- P-glycoprotein (P-gp), encoded by the ABCB1 (ATP-binding cassette transporter superfamily B member 1) gene, is a transport protein involved in the efflux and distribution of the osteosarcoma drugs me…
P-glycoprotein (P-gp), encoded by the ABCB1 (ATP-binding cassette transporter superfamily B member 1) gene, is a transport protein involved in the efflux and distribution of the osteosarcoma drugs methotrexate, doxorubicin, actinomycin D, and etoposide. In vivo studies indicate a close relationship between the ABCB1 (C1236T) single-nucleotide polymorphism (SNP) and the efficacy of these drugs. The purpose of this research was to elucidate the effect of ABCB1 (C1236T) polymorphism on P-gp-mediated efflux of osteosarcoma drugs. Two stable recombinant Caco-2 cell lines were generated by transfection with either the wild-type ABCB11236C allele or the ABCB11236T variant allele. The two cell lines were compared in terms of drug resistance, intracellular accumulation, and efflux of methotrexate, doxorubicin, actinomycin D, and etoposide. Accumulation of methotrexate, doxorubicin, actinomycin D, and etoposide was significantly lower in cells overexpressing wild-type P-gp than in untransfected control cells, indicating that these drugs are substrates of P-gp. Actinomycin D accumulated to similar extents in cells overexpressing wild-type or variant P-gp. Methotrexate and etoposide were transported to a greater extent by variant P-gp than wild-type protein. Conversely, doxorubicin was transported to a greater extent by wild-type P-gp. The ABCB1 (C1236T) polymorphism affects P-gp-mediated transport of osteosarcoma drugs in a drug-specific way. These studies support the importance of the ABCB1 (C1236T) SNP for P-gp activity and its potential to explain the alterations in drug response.
- Evaluation of the efficacy and toxicity of upper extremity isolated limb infusion chemotherapy for melanoma: An Australian multi-center study. [Multicenter Study]
- EJEur J Surg Oncol 2019; 45(5):832-837
- CONCLUSIONS: UL-ILI is safe to perform and effective, resulting in low limb toxicity. CR rates were similar to those for LL-ILI, but OR rates were lower for UL-ILI. It may be possible to improve OR rates achieved by UL-ILI by optimizing perioperative factors, while maintaining low toxicity.
- Can carboplatin or etoposide replace actinomycin-d for second-line treatment of methotrexate resistant low-risk gestational trophoblastic neoplasia? [Journal Article]
- GOGynecol Oncol 2019; 153(2):277-285
- CONCLUSIONS: Carboplatin did not have a satisfactory clinical response rate, likely due to severe hematological toxicity, which postponed chemotherapy. Our results reinforce the preference for Act-d as a second-line agent in patients with low-risk GTN after MTX/FA resistance.
- The coexistence of a Wilms' tumor and renal cell carcinoma in children: a case report and review of the literature. [Case Reports]
- OTOnco Targets Ther 2019; 12:953-958
- A combination of a Wilms' tumor (WT) and renal cell carcinoma (RCC) is an extremely rare pediatric renal neoplasm. Its prognosis and clinicopathological features remain unclarified. Herein, we descri…
A combination of a Wilms' tumor (WT) and renal cell carcinoma (RCC) is an extremely rare pediatric renal neoplasm. Its prognosis and clinicopathological features remain unclarified. Herein, we describe a case of the coexistence of a WT and an RCC in a male child aged 5 years and 10 months. The child had symptoms of hematuria for more than 1 month. Although his irises were clear, medical imaging revealed a potential malignant tumor in the left kidney. The patient underwent resection of the left kidney. The pathological diagnosis was the coexistence of a WT and papillary RCC. Negative surgical margins were examined. One month following the resection, chemotherapy with vincristine plus dactinomycin (EE-4A regimen) was commenced. At the 69-month follow-up, there was no recurrence or metastasis. The coexistence of a WT and an RCC in the pediatric population is considered a rare pathological event. At present, there is no standard treatment for these renal neoplasms. In this study, the RCC treatment, which was the same as that applied in cases of WTs, was reasonable.
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- Noninvasive monitoring of single-cell mechanics by acoustic scattering. [Journal Article]
- NMNat Methods 2019; 16(3):263-269
- The monitoring of mechanics in a single cell throughout the cell cycle has been hampered by the invasiveness of mechanical measurements. Here we quantify mechanical properties via acoustic scattering…
The monitoring of mechanics in a single cell throughout the cell cycle has been hampered by the invasiveness of mechanical measurements. Here we quantify mechanical properties via acoustic scattering of waves from a cell inside a fluid-filled vibrating cantilever with a temporal resolution of < 1 min. Through simulations, experiments with hydrogels and the use of chemically perturbed cells, we show that our readout, the size-normalized acoustic scattering (SNACS), measures stiffness. To demonstrate the noninvasiveness of SNACS over successive cell cycles, we used measurements that resulted in deformations of < 15 nm. The cells maintained constant SNACS throughout interphase but showed dynamic changes during mitosis. Our work provides a basis for understanding how growing cells maintain mechanical integrity, and demonstrates that acoustic scattering can be used to noninvasively probe subtle and transient dynamics.