Accumulation of Nucleolar Inorganic Polyphosphate Is a Cellular Response to Cisplatin-Induced Apoptosis.

The chemotherapeutic drug cisplatin, which targets DNA, serves as one of the main staples in cancer treatment. Yet, the therapeutic application of cisplatin is limited by two major challenges: the occurrence of reversible and irreversible side effects due to non-specific toxicity, and the intrinsic or developing resistance of tumor cells toward cisplatin. Here we demonstrate that cancer cells respond to cisplatin treatment with the nucleolar accumulation of inorganic polyphosphate (polyP), a universally conserved high-energy compound. PolyP accumulation positively correlates with the levels of activated caspase-3, suggesting a novel role of polyP in cisplatin-mediated apoptosis. In support of this finding, we discovered that administration of exogenous polyP increases cisplatin-induced toxicity in select cancer cell lines, raising the exciting possibility that enhancing endogenous polyP levels might be a novel mechanism to sensitize cancer cells to cisplatin treatment.

Comparison of first-line chemotherapy regimens for ovarian carcinosarcoma: a single institution case series and review of the literature.

BACKGROUND: The optimal first-line chemotherapy for ovarian carcinosarcoma has not yet been determined. We therefore sought to determine the progression-free survival (PFS) and overall survival (OS) for patients with ovarian carcinosarcoma treated at our institution with different first-line chemotherapy regimens. METHODS: This single-institution, retrospective analysis included all patients with ovarian or primary peritoneal carcinosarcoma diagnosed from September 1996 to July 2017. Kaplan Meier analysis with a log-rank Mantel-Cox test was used to compare PFS and OS between treatment groups, and a p-value of < 0.05 was considered statistically significant. RESULTS: Thirty-one patients met inclusion criteria: two patients were stage IC, 5 were stage II, 21 were stage III, and 3 were stage IV. The median PFS and OS for all stages was 9.3 and 19.7 months respectively. Fifteen patients (48%) received carboplatin/paclitaxel as first therapy, 7 (23%) received ifosfamide/paclitaxel, 6 (19%) received a different regimen, and 3 (10%) did not receive chemotherapy. Patients treated with carboplatin/paclitaxel had a statistically significant longer PFS when compared to those receiving ifosfamide/paclitaxel (17.8 vs. 8.0 months, p = 0.025). OS was similar between all comparisons. CONCLUSIONS: In summary, in our cohort of ovarian carcinosarcoma patients, median PFS is longer in patients treated with carboplatin/paclitaxel compared to ifosfamide/paclitaxel. Overall survival was similar for all treatment groups, potentially due to subsequent treatment crossover. Given the rarity and aggressive nature of this tumor, further study into optimal first-line chemotherapy is warranted.

Diagnostic Accuracy of Ultrasound, Contrast-enhanced CT, and Conventional MRI for Differentiating Leiomyoma From Leiomyosarcoma.

RATIONALE AND OBJECTIVES: This study aimed to determine whether uterine leiomyoma can be distinguished from uterine leiomyosarcoma on ultrasound (US), computed tomography (CT), and/or magnetic resonance imaging (MRI) without diffusion-weighted imaging. MATERIALS AND METHODS: Institutional review board approval was obtained and informed consent was waived for this Health Insurance Portability and Accountability Act-compliant retrospective case-control diagnostic accuracy study. All subjects with resected uterine leiomyosarcoma diagnosed over a 17-year period (1998-2014) at a single institution for whom pre-resection US (n = 10), CT (n = 11), or MRI (n = 7) was available were matched by tumor size and imaging modality with 28 subjects with resected uterine leiomyoma. Six blinded radiologists (three attendings, three residents) assigned 5-point Likert scores for the following features: (1) margins, (2) necrosis, (3) hemorrhage, (4) vascularity, (5) calcifications, (6) heterogeneity, and (7) likelihood of malignancy (primary end point). Mean suspicion scores were calculated and receiver operating characteristic curves were generated. The ability of individual morphologic features to predict malignancy was assessed with logistic regression. RESULTS: Mean suspicion scores were 2.5 ± 1.2 (attendings) and 2.4 ± 1.3 (residents) for leiomyoma, and 2.7 ± 1.3 (attendings) and 2.7 ± 1.4 (residents) for leiomyosarcoma. The areas under the receiver operating characteristic curves (range: 0.330-0.685) were not significantly different from chance, either overall (P = .36-.88) or by any modality (P = .28-.96), for any reader. Reader experience had no effect on diagnostic accuracy. No morphologic parameter was significantly predictive of malignancy (P = .10-.97). CONCLUSIONS: Uterine leiomyoma cannot be differentiated accurately from leiomyosarcoma on US, CT, or MRI without diffusion-weighted imaging.