BACKGROUND: Testicular cancer is associated with excellent prognosis and cure is achieved in most patients with advanced cancer treated with cisplatin-based chemotherapy. However, testicular cancer survivors are at increased risk of accelerated atherosclerosis, which significantly contributes to their late morbidity and mortality. Atherosclerosis is associated with a higher proportion of fat mass and especially with increased amount of visceral fat. We explored the effects of cisplatin-based chemotherapy on body composition during and after the treatment. PATIENTS AND METHODS: We studied 30 testicular cancer patients before chemotherapy, after the second cycle of chemotherapy and three months after the end of chemotherapy. Body composition parameters were evaluated using bioelectrical impedance analysis (BIA). RESULTS: Three months after the end of chemotherapy the fat mass had increased from 22.04±7.15% to 23.92±7.33% (P=0.026) and visceral fat volume had increased by 17% from 2.36±1.75l to 2.77±1.94l (P=0.013). In the whole sample there was a decrease in muscle mass after the second cycle of chemotherapy (-1.33 ± 2 kg on average; P=0.005). The changes in body composition varied according to distinct baseline fat mass. CONCLUSION: Cisplatin-based chemotherapy was associated with increase of fat mass, visceral fat, and body mass index. We also observed decrease in muscle mass and total body water. Our results suggest that BIA could help to target preventative measures to avert the acceleration of atherosclerosis in patients treated with cisplatin-based chemotherapy.

• Keywords
• bioelectrical impedance analysis, body composition, chemotherapy, fat mass, testicular cancer,
• MeSH
• Cisplatin therapeutic use   MeSH
• Electric Impedance MeSH
• Body Mass Index MeSH
• Humans MeSH
• Body Composition physiology   MeSH
• Testicular Neoplasms * drug therapy   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cisplatin MeSH

The checkpoint kinase 2 gene (CHEK2) codes for the CHK2 protein, an important mediator of the DNA damage response pathway. The CHEK2 gene has been recognized as a multi-cancer susceptibility gene; however, its role in non-Hodgkin lymphoma (NHL) remains unclear. We performed mutation analysis of the entire CHEK2 coding sequence in 340 NHL patients using denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA). Identified hereditary variants were genotyped in 445 non-cancer controls. The influence of CHEK2 variants on disease risk was statistically evaluated. Identified CHEK2 germline variants included four truncating mutations (found in five patients and no control; P = 0.02) and nine missense variants (found in 21 patients and 12 controls; P = 0.02). Carriers of non-synonymous variants had an increased risk of NHL development [odds ratio (OR) 2.86; 95% confidence interval (CI) 1.42-5.79] and an unfavorable prognosis [hazard ratio (HR) of progression-free survival (PFS) 2.1; 95% CI 1.12-4.05]. In contrast, the most frequent intronic variant c.319+43dupA (identified in 22% of patients and 31% of controls) was associated with a decreased NHL risk (OR = 0.62; 95% CI 0.45-0.86), but its positive prognostic effect was limited to NHL patients with diffuse large B-cell lymphoma (DLBCL) treated by conventional chemotherapy without rituximab (HR-PFS 0.4; 94% CI 0.17-0.74). Our results show that germ-line CHEK2 mutations affecting protein coding sequence confer a moderately-increased risk of NHL, they are associated with an unfavorable NHL prognosis, and they may represent a valuable predictive biomarker for patients with DLBCL.

• MeSH
• Checkpoint Kinase 2 genetics   MeSH
• Adult MeSH
• Genetic Predisposition to Disease * MeSH
• Genetic Association Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation MeSH
• DNA Mutational Analysis MeSH
• Lymphoma, Non-Hodgkin genetics   pathology   MeSH
• DNA Repair genetics   MeSH
• Prognosis * MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• RNA Splicing genetics   MeSH
• Germ Cells MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Checkpoint Kinase 2 MeSH
• CHEK2 protein, human MeSH Browser

UNLABELLED: The incidence and mortality of renal cell carcinoma (RCC) in the Czech Republic are among the highest in the world. Several targeted agents have been recently approved for the treatment of advanced/metastatic RCC. OBJECTIVE: Presentation of a national clinical database for monitoring and assessment of patients with advanced/metastatic RCC treated with targeted therapy. The RenIS (RENal Information System, http://renis.registry.cz ) registry is a non-interventional post-registration database of epidemiological and clinical data of patients with RCC treated with targeted therapies in the Czech Republic. Twenty cancer centres eligible for targeted therapy administration participate in the project. As of November 2011, six agents were approved and reimbursed from public health insurance, including bevacizumab, everolimus, pazopanib, sorafenib, sunitinib, and temsirolimus. As of 10 October 2011, 1,541 patients with valid records were entered into the database. Comparison with population-based data from the Czech National Cancer Registry revealed that RCC patients treated with targeted therapy are significantly younger (median age at diagnosis 59 vs. 66 years). Most RenIS registry patients were treated with sorafenib and sunitinib, many patients sequentially with both agents. Over 10 % of patients were also treated with everolimus in the second or third line. Progression-free survival times achieved were comparable to phase III clinical trials. The RenIS registry has become an important tool and source of information for the management of cancer care and clinical practice, providing comprehensive data on monitoring and assessment of RCC targeted therapy on a national level.

• MeSH
• Molecular Targeted Therapy MeSH
• Databases, Factual MeSH
• Carcinoma, Renal Cell drug therapy   mortality   MeSH
• Humans MeSH
• Kidney Neoplasms drug therapy   mortality   MeSH
• Antineoplastic Agents therapeutic use   MeSH
• Registries * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• Antineoplastic Agents MeSH

BACKGROUND: Rectal cancer accounts for approximately one third of all colorectal cancers (CRC), which belong among leading causes of cancer deaths worldwide. Standard treatment for locally advanced rectal cancer (cT3/4 and/or cN+) includes neoadjuvant chemoradiotherapy with fluoropyrimidines (capecitabine or 5-fluorouracil) followed by radical surgical resection. Unfortunately, a significant proportion of tumors do not respond enough to the neoadjuvant treatment and these patients are at risk of relapse. MicroRNAs (miRNAs) are small non-coding RNAs playing significant roles in the pathogenesis of many cancers including rectal cancer. MiRNAs could present the new predictive biomarkers for rectal cancer patients. METHODS: We selected 20 patients who underwent neoadjuvant chemoradiotherapy for advanced rectal cancer and whose tumors were classified as most sensitive or resistant to the treatment. These two groups were compared using large-scale miRNA expression profiling. RESULTS: Expression levels of 8 miRNAs significantly differed between two groups. MiR-215, miR-190b and miR-29b-2* have been overexpressed in non-responders, and let-7e, miR-196b, miR-450a, miR-450b-5p and miR-99a* have shown higher expression levels in responders. Using these miRNAs 9 of 10 responders and 9 of 10 non-responders (p < 0.05) have been correctly classified. CONCLUSIONS: Our pilot study suggests that miRNAs are part of the mechanisms that are involved in response of rectal cancer to the chemoradiotherapy and that miRNAs may be promising predictive biomarkers for such patients. In most miRNAs we identified (miR-215, miR-99a*, miR-196b, miR-450b-5p and let-7e), the connection between their expression and radioresistance or chemoresistance to inhibitors of thymidylate synthetase was already established.

• MeSH
• Adenocarcinoma genetics   metabolism   pathology   surgery   therapy   MeSH
• Capecitabine MeSH
• Chemoradiotherapy * MeSH
• Drug Resistance, Neoplasm genetics   MeSH
• Deoxycytidine analogs & derivatives   pharmacology   therapeutic use   MeSH
• Adult MeSH
• Fluorouracil analogs & derivatives   pharmacology   therapeutic use   MeSH
• Combined Modality Therapy MeSH
• Middle Aged MeSH
• Humans MeSH
• MicroRNAs biosynthesis   genetics   MeSH
• Neoplasm Proteins antagonists & inhibitors   physiology   MeSH
• Rectal Neoplasms genetics   metabolism   pathology   surgery   therapy   MeSH
• Neoadjuvant Therapy * MeSH
• Pilot Projects MeSH
• Antimetabolites, Antineoplastic pharmacology   therapeutic use   MeSH
• Gene Expression Regulation, Neoplastic * MeSH
• Retrospective Studies MeSH
• RNA, Neoplasm biosynthesis   genetics   MeSH
• Aged MeSH
• Gene Expression Profiling MeSH
• Thymidylate Synthase antagonists & inhibitors   physiology   MeSH
• Radiation Tolerance genetics   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• Capecitabine MeSH
• Deoxycytidine MeSH
• Fluorouracil MeSH
• MicroRNAs MeSH
• Neoplasm Proteins MeSH
• Antimetabolites, Antineoplastic MeSH
• RNA, Neoplasm MeSH
• Thymidylate Synthase MeSH

BACKGROUND: Annually, more than 27,000 persons die of cancer in the Czech Republic. It is known that in addition to the demographic aging of the Czech population, the cancer burden is increased. AIM: These data clearly demonstrate the need for affordable and good follow-up care for patients, especially for older patients and/or patients with no other cancer treatment due to irreversible progression of tumor. MATERIALS AND METHODS: We are talking about so-called palliative cancer care, which can be provided at different levels. One of the most common forms of palliative cancer care is hospice care. RESULTS: Our clinic in the years 2008-2010 received a total of 446 patients. 288 of them were women and 158 men. The average age of women was 61 years (age range 20-81 years). The average age of men was 56 years (age range 18-96 years). The performance status was in the fitness category PS-0 (8%), PS-1 (54%), PS-2 (33%) and PS-3 (5%). CONCLUSION: Currently the outpatient palliative cancer care are coming more into the forefront. This type of care allows patients to stay as long as possible at home among their close relatives. Prerequisite for a well working outpatient palliative care is cooperation with general practitioners and home health care agencies.

• Keywords
• Elderly patient, Geriatric oncology, Outpatient palliative cancer care, Quality of life,
• Publication type
• Journal Article MeSH

BACKGROUND: Colorectal cancer (CRC) represents a serious health care problem in the Czech Republic, introducing a need for a prospective modelling of the incidence and prevalence rates. The prevalence of patients requiring anti-tumour therapy is also of great importance, as it is directly associated with planning of health care resources. METHODS: This work proposes a population-based model for the estimation of stage-specific prevalence of CRC patients who will require active anti-tumour therapy in a given year. Its applicability is documented on records of the Czech National Cancer Registry (CNCR), which is used to estimate the number of patients potentially treated with anti-tumour therapy in the Czech Republic in 2015. RESULTS: Several scenarios are adopted to cover the plausible development of the incidence and survival rates, and the probability of an anti-tumour therapy initiation. Based on the scenarios, the model predicts an increase in CRC prevalence from 13% to 30% in comparison with the situation in 2008. Moreover, the model predicts that 10,074 to 11,440 CRC patients will be indicated for anti-tumour therapy in the Czech Republic in 2015. Considering all patients with terminal cancer recurrence and all patients primarily diagnosed in stage IV, it is predicted that 3,485 to 4,469 CRC patients will be treated for the metastatic disease in 2015, which accounts for more than one third (34-40%) of all CRC patients treated this year. CONCLUSIONS: A new model for the estimation of the number of CRC patients requiring active anti-tumour therapy is proposed in this paper. The model respects the clinical stage as the primary stratification factor and utilizes solely the population-based cancer registry data. Thus, no specific hospital data records are needed in the proposed approach. Regarding the short-term prediction of the CRC burden in the Czech Republic, the model confirms a continuous increase in the burden that must be accounted for in the future planning of health care in the Czech Republic.

• MeSH
• Child MeSH
• Adult MeSH
• Infant MeSH
• Colorectal Neoplasms drug therapy   epidemiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Forecasting MeSH
• Child, Preschool MeSH
• Antineoplastic Agents therapeutic use   MeSH
• Registries * MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• Antineoplastic Agents MeSH

In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syndromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

• Keywords
• Diabetes, Molecular biology, Pancreatic cancer, Pancreatitis, Risk factors,
• MeSH
• Pancreatitis, Chronic epidemiology   etiology   genetics   physiopathology   MeSH
• Diabetes Mellitus epidemiology   genetics   MeSH
• Diagnosis, Differential MeSH
• Genetic Predisposition to Disease MeSH
• Comorbidity MeSH
• Humans MeSH
• Survival Rate MeSH
• Molecular Biology * MeSH
• Pancreatic Neoplasms epidemiology   etiology   genetics   physiopathology   MeSH
• Risk Factors MeSH
• Signal Transduction physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH