1.
Response to olaparib in a PALB2 germline mutated prostate cancer and genetic events associated with resistance.
Horak, P, Weischenfeldt, J, von Amsberg, G, Beyer, B, Schütte, A, Uhrig, S, Gieldon, L, Klink, B, Feuerbach, L, Hübschmann, D, et al
Cold Spring Harbor molecular case studies. 2019;(2)
Abstract
Prostate cancers harboring DNA repair gene alterations are particularly sensitive to PARP inhibitor treatment. We report a case of an advanced prostate cancer patient profiled within the NCT-MASTER (Molecularly Aided Stratification for Tumor Eradication Research) precision oncology program using next-generation sequencing. Comprehensive genomic and transcriptomic analysis identified a pathogenic germline PALB2 variant as well as a mutational signature associated with disturbed homologous recombination together with structural genomic rearrangements. A molecular tumor board identified a potential benefit of targeted therapy and recommended PARP inhibition and platinum-based chemotherapy. Single-agent treatment with the PARP inhibitor olaparib as well as subsequent combination with platinum-based chemotherapy resulted in disease stabilization and substantial improvement of clinical symptoms. Upon progression, we performed whole-exome and RNA sequencing of a liver metastasis, which demonstrated up-regulation of several genes characteristic for the neuroendocrine prostate cancer phenotype as well as a novel translocation resulting in an in-frame, loss-of-function fusion of RB1. We suggest that multidimensional genomic characterization of prostate cancer patients undergoing PARP inhibitor therapy will be necessary to capture and understand predictive biomarkers of PARP inhibitor sensitivity and resistance.
2.
Low-dose imatinib in the treatment of severe systemic sclerosis: a case series of six Chinese patients and literature review.
Guo, L, Chen, XX, Gu, YY, Zou, HJ, Ye, S
Clinical rheumatology. 2012;(9):1395-400
Abstract
Systemic sclerosis (SSc) is a progressive fibrotic disorder with no legitimate effective treatment. Several clinical trials had investigated imatinib mesylate with a target dose of 400∼600 mg/day on SSc, and the efficacy is controversial with a generally poor tolerability. We herein reported six female Chinese patients with SSc administered with low-dose imatinib (200 mg/day) for a median of 23 months (10∼30 months). Patients displayed a decreased modified Rodman skin scores (mRSS) by a mean of 6.29 points after 6 months of treatment. Three patients who completed 2 years of treatment achieved a reduction of mRSS by 8, 18, and 30.5 points, respectively. Pulmonary function was improved or stabilized in two patients with interstitial lung disease. Severe gastrointestinal involvement in one patient was attenuated in terms of discontinuation of total parenteral nutrition and restoration of the serum albumin level. Imatinib was well-tolerated in general, although there were two severe adverse events: a bone fracture and a cerebral hemorrhage in two individuals. Both the adverse events were probably not directly related to imatinib and were recovered uneventfully. Our limited data, along with the review of the literature, suggested that low-dose imatinib might be effective and better tolerated in severe SSc that deserves further study.
3.
Suppression of non-sustained ventricular tachycardia with ranolazine: a case report.
Kaliebe, JW, Murdock, DK
WMJ : official publication of the State Medical Society of Wisconsin. 2009;(7):373-5
Abstract
BACKGROUND Ranolazine is a new anti-anginal agent that inhibits abnormal late sodium currents, indirectly causing a decrease in diastolic cardiomyocyte calcium levels. This produces an energy-sparing effect and stabilizes cardiac membranes. Ranolazine has been shown to be a potent inhibitor of triggered activity in the experimental setting. METHODS This case report describes the dramatic antiarrhythmic effects of ranolazine in a patient with highly symptomatic complex ventricular ectopy, including non-sustained ventricular tachycardia (NSVT). Cardiac ischemia and left ventricular systolic dysfunction were ruled out by cardiac catheterization. After failing standard treatment, we initiated ranolazine therapy. RESULTS Ranolazine was effective in suppressing ectopic ventricular activity and completely suppressed NSVT. CONCLUSIONS Further research on the anti-arrhythmic properties of ranolazine in the clinical setting is needed.
4.
[Gastrointestinal stromal tumor of small intestine associated with lymph node metastasis: a report of 2 cases with review of literatures].
Kong, M, Wang, YL, Xu, LJ, Teng, XD
Zhonghua bing li xue za zhi = Chinese journal of pathology. 2009;(9):617-20
Abstract
OBJECTIVE To study the clinicopathologic features of gastrointestinal stromal tumor (GIST) of small intestine with lymph node metastasis and evaluate the respond to imatinib mesylate (Glivec) therapy. METHODS Two cases of GIST of small intestine associated with lymph node metastasis were collected and investigated by light microscopy and immunohistochemistry. Mutation in exon 9, 11 and of c-kit gene were analyzed by polymerase chain reaction and DNA sequencing. RESULTS The cases presented as small intestinal mass of irregular shape. Histologically, the tumors consisted of epithelioid and spindled cells, with areas of coagulative necrosis and hemorrhage. The mitotic count measured about 2 per 50 high-power fields. Immunohistochemical study showed that the tumor cells were diffusely distributed and strongly positive for CD117. Mutation analysis revealed that case 1 had an in-frame deletion of 11 amino-acid residues corresponding to 559-569 and carried two missense mutations involving codons 570, 571 in exon 11 of c-kit gene. Case 2 revealed an in-frame deletion involved condons 559-565 in exon 11 of c-kit gene. These two cases were all underwent primary chemotherapy with imatinib mesylate and without new tumor was found during follow-up periods (18, 26 months) after operation. CONCLUSIONS GIST with nodal metastasis is very rare and needs to be distinguished from other soft tissue sarcomas occurring in this site. The responsiveness to imatinib mesylate therapy correlates with the mutation status of c-kit gene.
5.
Imatinib-induced tumor lysis syndrome: report of a case and review of the literature.
Chang, H, Shih, LY
Chang Gung medical journal. 2008;(5):510-4
Abstract
Imatinib is a selective tyrosine kinase inhibitor which acts on breakpoint cluster region-Abelson fusion gene (BCR-ABL) positive leukemia including all phases of chronic myeloid leukemia and acute lymphoblastic leukemia. It may induce rapid apoptosis and subsequent tumor lysis syndrome. Only 3 cases of imatinib-induced tumor lysis syndrome have been reported. We herein described an additional patient with BCR-ABL (ela2) positive acute lymphoblastic leukemia who developed tumor lysis syndrome after 10-day treatment with imatinib. Experience in the current case suggests that preventive measures for tumor lysis syndrome, including allopurinol and hydration, should be taken for patients with high leukemia burden who receive imatinib therapy, and parameters of tumor lysis should be monitored in the early phase of therapy.