- [Treatment Outcomes of Adult-Onset Ewing Sarcoma: A Single-Center Retrospective Study of Five Cases]. [English Abstract, Journal Article]
- Gan To Kagaku Ryoho 2016 Aug; 43(8):1015-8.
We report the treatment outcomes of 5 cases of adult-onset Ewing sarcoma(ES)managed between 2011 and 2014. We examined prognostic factors including the primary lesion, tumor size, metastatic status, and serum LDH levels.The locations of the primary lesions included the limbs in 1 case and the trunk in 4; the cases in the trunk had a worse prognosis than that in the limbs. Tumor size was greater than 8 cm in only 1 patient, who also displayed evidence of metastases at presentation and high LDH levels. All the patients received chemotherapy consisting of alternating vincristine, doxorubicin, and cyclophosphamide(VDC)and etoposide and ifosfamide(IE). Surgery was selected for the treatment of 4 patients, and radiotherapy was administered to 1 patient for local treatment of the tumor. A median follow-up duration of 31.6 months revealed the 2-year overall survival rate and progression-free survival rate to be 80.0%.The prognosis of patients with adult-onset ES is poor; however, combined modality therapy, including VDC-IE, was demonstrated to improve the outcome of patients in the present study. Nevertheless, the patient with tumor size exceeding 8 cm, metastasis, and high LDH levels, relapsed 1 year after treatment, as reported previously. Further investigation is required to clarify the factors affecting prognosis in adults, and to develop effective therapies for patients with a poor prognosis.
- Primary yolk sac tumor of the gluteus: a case report and literature review. [Journal Article]
- Onco Targets Ther 2016.:4715-9.
Yolk sac tumor (YST) is a common malignant primitive germ cell tumor that often exhibits differentiation into endodermal structures. They most commonly occur in childhood and adolescence and are rare after the age of 40 years. Derived from the yolk sac during the embryonic period, YSTs can occur in the gonads and germ cells because the tumor cells migrate from the yolk sac toward the gonads. Here, we present a rare case of primary gluteus YST in a 3-year-old girl. She received BEP chemotherapy (bleomycin + etoposide + cisplatin) after surgical resection. There was no evidence of recurrence 7 months after primary treatment.
- Small Cell Lung Cancer. [Journal Article]
- Cancer Treat Res 2016.:301-22.
Small cell lung cancer (SCLC) is an aggressive cancer of neuroendocrine origin, which is strongly associated with cigarette smoking. Patients typically present with a short duration of symptoms and frequently (60-65 %) with metastatic disease. SCLC is a heterogeneous disease including extremely chemosensitive and chemoresistant clones. For this reason, a high percentage of patients respond to first-line chemotherapy but rapidly succumb to the disease. SCLC is generally divided into two stages, limited and extensive. Standard treatment of limited stage disease includes combination chemotherapy with cisplatin and etoposide for four cycles, thoracic radiation initiated early with the first cycle of chemotherapy, and consideration of prophylactic cranial irradiation (PCI) in the subset of patients with good response. Surgery may play a role in TNM stages I and II. In extensive disease, platinum agents and etoposide, used in combination, are again the first-line standard of care in the USA. However, thoracic radiation therapy is used predominately in patients where local control is important and PCI is of uncertain benefit. Despite these treatments, prognosis remains poor and novel therapies are needed to improve survival in this disease.
- Emerging trends in the evaluation and management of small cell prostate cancer: A clinical and molecular perspective. [JOURNAL ARTICLE]
- Expert Rev Anticancer Ther 2016 Aug 18.
Prostatic small cell carcinoma (PSCC) is a rare, aggressive form of prostate cancer associated with poor clinical outcomes. It can arise de novo or in the setting of castrate resistant adenocarcinoma of the prostate. Current therapeutic interventions are based upon observations the PSCC responds similarly to small cell carcinoma of the lung. Standard treatment includes chemotherapy with cisplatin and etoposide, radiation therapy, and occasional extirpative management. Ongoing research into the molecular pathway behind the development of PSCC and potential interventions is resulting in the identification of multiple novel therapeutic targets.A review of contemporary literature was undertaken to evaluate the histology, pathogenesis, evolution, current and novel treatment regimens, and upcoming methods of diagnosis of PSCC. To this end a literature search using terms, "prostate small cell carcinoma", "neuroendocrine prostate cancer", and derivations thereof was performed with a thorough review of the current literature. Expert Commentary: Among current studies, AURKA inhibitors and PAPR1 inhibitors are exciting potential targets with early studies suggesting significant benefit. Continued research into the molecular underpinnings of PSCC is necessary to identify novel targets for early identification of patients with PSCC and to develop optimal treatment regimens.
- A Two-Mechanism Model for the Interaction of Etoposide Quinone with Topoisomerase IIα. [JOURNAL ARTICLE]
- Chem Res Toxicol 2016 Aug 17.
Topoisomerase II is an essential nuclear enzyme involved in regulating DNA topology to facilitate replication and cell division. Disruption of topoisomerase II function by chemotherapeutic agents is in use as an effective strategy to fight cancer. Etoposide is an anticancer therapeutic that disrupts the catalytic cycle of topoisomerase II and stabilizes enzyme-bound DNA strand breaks. Etoposide is metabolized into several species including active quinone and catechol metabolites. Our previous studies have explored some of the details of how these compounds act against topoisomerase II. In our present study, we extend those analyses by examining several effects of etoposide quinone on topoisomerase IIα including whether the quinone impacts ATP hydrolysis, DNA ligation, cleavage complex persistence, and enzyme:DNA binding. Our results demonstrate that the quinone inhibits relaxation at 100-fold lower levels of drug when compared to etoposide. Further, the quinone inhibits ATP hydrolysis by topoisomerase IIα. The quinone does appear to stabilize single-strand breaks similar to etoposide suggesting a traditional poisoning mechanism. However, there is minimal difference in cleavage complex persistence in the presence of etoposide or etoposide quinone. In contrast to etoposide, we find that etoposide quinone blocks enzyme:DNA binding, which provides an explanation for previous data showing the ability of the quinone to inactivate the enzyme over time. Finally, etoposide quinone is able to stabilize the N-terminal protein clamp implying an interaction between the compound and this portion of the enzyme. Taken together, the evidence supports a two-mechanism model for the effect of the quinone on topoisomerase II: 1) interfacial poison and 2) covalent poison that interacts with the N-terminal clamp and impacts the binding of DNA.
- Pneumatosis intestinalis after etoposide-based chemotherapy in a patient with metastatic small cell lung cancer: successful conservative management of a rare condition. [JOURNAL ARTICLE]
- Einstein (Sao Paulo) 2016 Aug 15.:0.
A 69-year-old male patient, smoker, was diagnosed with small cell lung cancer metastatic to lung, liver and central nervous system. He received chemotherapy with carboplatin AUC 5 on day 1 and etoposide 100mg/m2 on days 1, 2 and 3. During the first cycle, the patient presented with febrile neutropenia and abdominal distension. Chest, abdomen and pelvis computed tomography scan was performed and detected gas dissecting the wall of sigmoid colon extending to the mesosigmoid. Patient had no abdominal pain, nausea, vomiting, and on physical examination he had no peritoneal irritation, tachycardia or hemodynamic instability compatible with perforation or acute abdomen. Therefore, the radiological finding was interpreted as pneumatosis intestinalis caused by chemotherapy with etoposide. Pneumatosis resolved after continuous oxygen therapy. The second cycle was administered after a complete resolution of the clinical condition and etoposide dose was reduced by 30%. The patient experienced a remarkable evolution. RESUMO Paciente do gênero masculino, 69 anos, fumante, diagnosticado com câncer de pulmão de pequenas células, metastático para pulmão, fígado e sistema nervoso central. Foi administrada quimioterapia com carboplatina AUC 5 no dia 1 e etoposídeo 100mg/m2 nos dias 1, 2 e 3. Durante o primeiro ciclo, o paciente apresentou neutropenia febril e distensão abdominal. Tomografias de tórax, abdome e pelve detectaram gás dissecando a parede do cólon sigmoide, com extensão para o mesossigmoide. O paciente não apresentava dor abdominal, náusea, vômito e não tinha sinais de irritação peritoneal, taquicardia ou instabilidade hemodinâmica compatíveis com perfuração ou abdome agudo. O achado radiológico foi interpretado como pneumatose intestinal causada por etoposídeo. A resolução do quadro ocorreu após suplementação de oxigênio. O segundo ciclo foi administrado após resolução completa do quadro, com redução da dose do quimioterápico em 30%. O paciente evoluiu de forma bastante satisfatória.
- [Outcome Comparison of Pediatric Langerhans Cell Histiocytosis Treated with Modified DAL-HX83/90 or JLSG-96 Protocol]. [English Abstract, Journal Article]
- Zhongguo Shi Yan Xue Ye Xue Za Zhi 2016 Aug; 24(4):1190-5.
To analyze and compare the clinical features, treatment and prognosis of 31 children with Langerhans cell histiocytosis(LCH) treated with modified DAL-HX83/90 or JLSG-96 protocol.The clinical features, treatment and prognosis of 31 children with Langerhans cells admitted in our hospital from January 2005 to December 2014 were analyzed retrospectively. The outcome of patients treated with modified DAL-HX83/90 or JLSG-96 protocols were compared by using the Kaplan-Meier survival curve. Among 31 children with LCH, 19 males and 12 females, 12 younger than 2 years old, and 19 older than 2 years old. LCH usually affected skeleton system(77.4%), skin(42.0%), liver(29.0%), spleen(19.4%), hematopoietic system(12.9%). The most common misdiagnoses were upper respiratory tract infection, malignancies, focal infection, and eczema.Response rate at week 6 was 76.9% in modified DAL-HX83/90 group and 94.1% in JLSG-96 group respectively, and no significant differences had been found between 2 groups. The 1-and 3-year overall survival rates of the patients treated with JLSG-96 protocol were 100% and 83.3%±15.2% respectively, while The 1-, 3-,5-year overall survival rates of those patients treated with the modified DAL-HX83/90 protocol were 70%±14.5%. The 1-and 3-year event-free rates of children treated with JLSG-96 protocol were 73.3%±11.4% and 66.7%±12.2%, respectively, while the 1-, 3-, 5-year event-free rates of those treated with modified DAL-HX83/90 protocol were 50%±15.8%, 40%±15.6% and 26.7%±15% respectively. No differences were found between the 2 groups for OS or EFS.JLSG-96 protocol shows a better prognosis, and the risk of secondary malignancy caused by etoposide can be avoided. Early diagnosis of refractory LCH, specified grouping strategy and prolonged maintenance therapy may contribute to enhancing the EFS rates and reducing relapses.
- [Genetic variation in DNA repair gene RAD52 is associated with the response to platinum-based chemotherapy in SCLC patients]. [English Abstract, Journal Article]
- Zhonghua Zhong Liu Za Zhi 2016 Jul; 38(7):504-9.
To explore the associations between genetic variations of DNA repair gene RAD52 and response to platinum-based chemotherapy of small cell lung cancer (SCLC), and to analyze the influencing factors on survival.Nine haplotype-tagging single nucleotide polymorphisms (htSNPs) of RAD52 were genotyped by Sequenom Mass ARRAY technology in 939 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between genotypes and platinum-based chemotherapy response were analyzed by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for sex, age, smoking, KPS, staging and chemotherapy regimens, by unconditional logistic regression model. The relative ratios (RRs) were estimated using Cox proportional hazards regression model.Among the 939 cases, 483 (51.4%) cases received cis-platinum and etoposide treatment while others treated with carboplatin and etoposide. Six hundred and eighty two patients were chemotherapy responders in the study with a response rate of 72.6%. Patients were followed up to get their survival information. The median survival time (MST) of these patients was 25 months. We found that rs10774474 SNP which located in the 5'-flanking region of RAD52 was significantly associated with chemotherapy response. Compared with the TT genotype, patients with TA and AA genotype had a worse chemotherapy response and increased risk of no-response (P=0.004). Correlation analysis showed that patients with KPS >80 had a better chemotherapy response than those with KPS≤80 (P=0.001). The patients with extensive-stage had a worse chemotherapy response than those with limited-stage (P<0.001). Cox proportional hazards regression model analysis showed that nine htSNPs of RAD52 were not associated with the overall survival (OS) of SCLC patients who received platinum-based chemotherapy. Age≤56, KPS>80, limited-stage, chemotherapy response and radiation therapy can remarkably prolong OS (allP<0.05).These results suggest that RAD52 genetic polymorphism rs10774474 plays an important role in the response to platinum-based chemotherapy, and may be a potential genetic biomarker for SCLC personalized treatment.
- Comparison of the efficiency of ABVD versus BEACOPP for Hodgkin lymphoma treatment: a meta-analysis. [REVIEW, JOURNAL ARTICLE]
- Int J Hematol 2016 Aug 16.
To compare the efficiency of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) against that of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) for treating Hodgkin lymphoma (HL). An extensive English-language literature retrieval on clinical outcomes after treatment by ABVD versus BEACOPP was conducted on Medline, PubMed, and Embase through the period ending December 2015. Odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was pooled based on the heterogeneity across individual studies. In total, seven articles reporting on four trials were included in this meta-analysis. Patients assigned to BEACOPP therapy had a better complete remission (CR) rate (OR = 0.55, 95 % CI 0.35, 0.87), overall survival (OS) greater than 5 years (OR = 0.64, 95 % CI 0.51, 0.81), and progression-free survival (PFS, OR = 0.56, 95 % CI 0.38, 0.81) than patients assigned to ABVD therapy. Subgroup analysis stratified using a different strategy showed no significant difference for OS between short courses of escalated BEACOPP combined with standard BEACOPP and that for ABVD (OR = 0. 72, 95 % CI 0. 45, 1.15). Reduced progression/relapse, better CR, and similar OS were observed with BEACOPP, indicating its superior efficiency of BEACOPP in the treatment of HL. However, more analysis of treatment-related toxicity is needed.
- Highly activated p53 contributes to selectively increased apoptosis of latently HIV-1 infected cells upon treatment of anticancer drugs. [Journal Article]
- Virol J 2016; 13(1):141.
Despite the successful inhibition of human immunodeficiency virus type 1 (HIV-1) replication by combination antiretroviral therapy, cells latently infected with HIV-1 remaining in patients are a major obstacle for eradication of HIV-1 infection. The tumor suppressor factor p53 is activated by HIV-1 infection, and restricts HIV-1 replication. However, a therapeutic strategy based on p53 activity has not been considered for elimination of latently infected cells.Apoptotic cells were analyzed using flow cytometry with anti-annexin A5-FITC Ab and PI staining upon treatment of anticancer drugs. The expression and activation of p53 and apoptotic molecules in latently HIV-1-infected T cells were compared using Western blot analysis. The role of p53 in the anticancer drug treatment-induced apoptosis of cells latently infected with HIV-1 was determined by knock-down experiment using siRNA against p53.Upon treatment with 5-fluorouracil (5-FU), apoptosis was increased in latently infected ACH2 cells encoding competent p53 compared with uninfected parent A3.01 cells, while the apoptosis of latently infected p53 null J1.1 cells was less than that of uninfected cells. Treatment with 5-FU increased the levels of cleaved caspase-3 and PARP in ACH2 cells compared with uninfected and latently infected p53 null J1.1 cells. The levels of expression and activation of p53 were higher in both latently infected ACH2 and NCHA2 cells than in uninfected cells. Furthermore, the activation levels of p53 in both cells were further increased upon 5-FU treatment. Consistent with p53 status, apoptosis was markedly increased in ACH2 and NCHA2 cells compared with uninfected and latently infected J1.1 cells upon treatment with other anticancer drugs such as doxorubicin and etoposide. Inhibition of p53 in cells with latent HIV-1 infection diminished apoptosis upon 5-FU treatment.Evidence described here indicate that when treated with anticancer drugs, apoptosis of cells with latent HIV-1 infection was increased via the p53 activation pathway and may provide information for application of anticancer drugs to selectively eliminate HIV-1 reservoirs.