Excision Repair Cross-Complementation Group 1 Enzyme as a Molecular Determinant of Responsiveness to Platinum-Based Chemotherapy for non Small-Cell Lung Cancer

Although platinum-based chemotherapy remains the “standard” in advanced non small-cell lung cancer, not all patients derive clinical benefit from such a treatment. Hence, the development of predictive biomarkers able to identify lung cancer patients who are most likely to benefit from cisplatin-based chemotherapy has become a scientific priority. Among the molecular pathways involved in DNA damage control after chemotherapy, the nucleotide excision repair (NER) is a critical process for the repair of DNA damage caused by cisplatin-induced DNA adducts. Many reports have explored the role of the excision repair cross-complementation group 1 enzyme (ERCC1) expression in the repair mechanism of cisplatin-induced DNA adducts in cancer cells

Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update.

PURPOSE: To update the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. METHODS: PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer due to limited RCT evidence in the cancer setting. ASCO and ASH convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS: The primary literature review included 15 meta-analyses of RCTs and two RCTs. A growing body of evidence suggests that adding iron to treatment with an ESA may improve hematopoietic response and reduce the likelihood of RBC transfusion. The biosimilar literature review suggested that biosimilars of epoetin alfa have similar efficacy and safety to reference products, although evidence in cancer remains limited. RECOMMENDATIONS: ESAs (including biosimilars) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to \u3c 10 g/dL. RBC transfusion is also an option. With the exception of selected patients with myelodysplastic syndromes, ESAs should not be offered to most patients with nonchemotherapy-associated anemia. During ESA treatment, hemoglobin may be increased to the lowest concentration needed to avoid transfusions. Iron replacement may be used to improve hemoglobin response and reduce RBC transfusions for patients receiving ESA with or without iron deficiency. Additional information is available at www.asco.org/supportive-care-guidelines and www.hematology.org/guidelines

EXPERIENCES OF DRUG USERS IN IIA CLASS JAIL YOGYAKARTA

United Nations Office on Drugs and Crime (UNODC) estimated that about 149-272 million people or 3.3 % - 6.1 % of world population aged 15-64 years used drugs (even once) during their life time. This estimation will increase with time (BNN, 2011). The number of prisoners suffering HIV/AIDS in recent years were increasing as well if compared to its numbers in the year 2011 from 787 people to 1042 people. It was estimated that in the year 2015, the number of drug users in Indonesia would increase to 5.8 million people, since the number of drug users at the present time were reached 4 million people. For the time being, in Yogyakarta second A class drug jail , the number of drug users were 256 people; this number were constant; its mean that if there was prisoner got his / her freedom, another prisoner was incoming. Data from BNN in August 2013 years, 70% of 4 million drug users in Indonesia were workers (productive aged). Aim; To discovered population research experiences that cause them used drugs and depend on its. Research method: This was qualitative research with phenomenological approach. Data gathering technique were deep interview and FGD toward 30 respondents. Data were analyzed using reduction, data display, and conclusion drawing/verification. The majority of respondents mentioned that they used drugs because of they wanted to know and the influence of friends. Drugs, kinds of sabu, used to increase energy and ganja were used to obtain peacefulness. Drugs users wanted to use its forever; therefore, they wanted to stop because of punishment to be in jail not because of the drugs had negative effects to the body. The majority of respondents mentioned that to stop using drugs must be self motivated; on the contrary, the obstacle to stop using drugs because of missing sensation to use it. They named it suggest. Using drugs were conducted by research population because of environmental influence, to increase energy and to obtain peacefulness. Keywords : The experiences of drug use

Concurrent development of testicular seminoma and choriocarcinoma of the superior mediastinum, presented as cervical mass: a case report and implications about pathogenesis of germ-cell tumours

BACKGROUND: Synchronous presentation of more than one germ cell tumours of different histology in the same patient is considered to be very rare. In these cases of multiple germ cell tumours, strong theoretical and clinical data suggest an underlying common pathogenetic mechanism concerning genetic instability or abnormalities during the pluripotent embryonic differentiation and maturation of the germ cell. CASE PRESENTATION: A 25 year-old young man presented with an enlarging, slightly painful left cervical mass. Despite the initial disorientation of the diagnosis to a possible thyroid disorder, the patient underwent complete surgical resection of the mass revealing mediastinal choriocarcinoma. Subsequent ultrasound of the scrotum indicated the presence of a small lobular node in the upper pole of the left testicle and the patient underwent radical left inguinal orchiectomy disclosing a typical seminoma. Based on these results, the patient received 4 cycles of Bleomycin, Etoposide and Platinum chemotherapy experiencing only mild toxicity and resulting in complete ongoing clinical and biochemical remission. CONCLUSION: The pathogenesis of concurrent germ cell tumours in the same patient remains an area of controversy. Although the genetic instability of the pluripotent germ cell offers an adequate explanation, the possibility of metastasis from the primary, less differentiated tumour to a distant location as a more mature subtype cannot be excluded. Possible development of a metastatic site of different histology and thus biological behaviour (e.g choriocarcinoma) should be anticipated. Furthermore, urologists, pathologists and medical oncologists should be meticulous in the original pathological diagnosis in these patients, since there is a significant frequency of germ cell tumours with mixed or overlapping histological elements with diverse potential of evolution and differentiation

Making progress in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer by surpassing resistance: third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs)

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) represent the standard of care for advanced non-small cell lung cancer (NSCLC) patients whose tumours harbor an activating EGFR mutation. Unfortunately, resistance to first-and second-generation EGFR-TKIs inevitably occurs in all patients with EGFR-mutant disease approximately within a year of treatment. At least half of these cases are attributed to the emergence of a secondary mutation in exon 20 of the EGFR gene, namely the T790M mutation. Third-generation EGFR-TKIs, including osimertinib and rociletinib, target this epigenic mutation, thus re-sensitizing cancer cells to EGFR-TKI inhibition. Osimertinib to date represents the standard of care in EGFR-mutant tumors after failure of first-line EGFR-TKIs by over-performing platinum-based chemotherapy in the recently reported AURA-3 randomized phase III clinical trial. The aim of this review is to describe the different treatment strategies that have been developed to reverse resistance to first-and second-line EGFR-TKIs, the corresponding mechanisms of resistance and the development of novel-generation EGFR-TKIs. We also discuss the challenge posed by the implementation of third-generation EGFR-TKIs earlier in the course of the disease in first-line treatment of EGFR-mutant NSCLC

Markers of bone remodeling, osteoclastic activity and angiogenesis in patients with solid tumours metastatic to the skeleton

Background: Receptor Activator of Nuclear factor KappaΒ Ligand (RANKL) and its endogenous inhibitor osteoprotegerin (OPG) are important determinants of bone remodeling in patients with solid tumors metastatic to the skeleton. We aimed: a) to assess the levels of the RANKL/OPG system and of a panel of biochemical markers in patients with solid tumors metastatic to the bone in relation to the type of malignancy and the neoplastic burden to the skeleton b) to evaluate the effect of treatment with the biphosphonate zoledronic acid on markers of bone remodeling and c) to detect possible correlations of marker response with skeletal morbidity and clinical outcomes. Patients and Methods: Levels of soluble RANKL (sRANKL), OPG and RANKL/OPG ratio were assessed in 70 patients with breast (N=30), lung (N=18) and prostate (N=22) cancer with newly-diagnosed metastasis to the bone and in 40 healthy age and sex-matched volunteers. Biochemical markers of bone resorption, including C-telopeptide of type-I collagen (CTX), tartrate-resistant acid phosphatase-5b (TRACP-5b) and osteopontin (OPN) and of bone formation, including bone-alkaline phosphatase (bALP), osteocalcin (OC), and C-terminal propeptide of collagen type-I (CICP) were also assessed at the onset of skeletal metastases and six months after initiation of treatment with zoledronic acid (4 mg monthly). Logistic regression models were applied to assess the correlation between bone marker level changes and Skeletal Related Events (SRE, primary endpoint), recurrence and death. Results: Patients had elevated serum levels of RANKL, OPG, OPN, TRACP-5b, and bALP, and reduced OC levels compared to controls. OPG correlated with the extend of metastatic bone burden. Patients with breast and lung cancer shared increased levels of RANKL, OPG, and OPN whereas prostate cancer patients had elevated values of OPG and bALP only. After a median follow-up of 32 months, 34 patients (48.6%) presented with at least one SRE and 48 patients (68.6%) relapsed. RANKL/OPG ratio tended to decline after treatment with zoledronic acid with the exception of patients with prostate cancer. CTX levels were significantly reduced in the whole study population at the second compared to the initial measurement (p=0.003). Decrease in TRACP-5b levels tended to correlate with reduced incidence of SRE (HR=0.39, 95%CI: 0.14-1.10, p=0.076) and the model fit was improved when Performance Status (PS) at diagnosis was added in logistic regression analysis (p=0.051). Tumor type (lung or breast vs prostate) and PS (PS³2 vs <2) were the only significant predictors for recurrence and death and none of the bone markers was able to improve predictive value when added to the model. Conclusions: Patients with solid tumors metastatic to the bone have severe disruption of the RANKL/OPG axis. Breast and lung cancer seem to exert their osteolytic action through upregulation of the RANKL/OPG system whereas prostate cancer seems to provoke profound elevation of OPG levels only, thus leading to increased osteoblastic activity. Imbalance in the RANKL/OPG axis tends to normalize after treatment with zoledronic acid, as reflected by decrease in serum bone resorption markers. Marker level responses are not predictive for SRE, disease progression or survival