Ciência e terapia do câncer

Genetic variants of transforming growth factor beta receptors type-1 (TGF-βR1) are involved in cellular signalling pathway and their mutations encoded amino acids involved in protein structure has not been defined. Present study evaluate the frequency of TGF-βR1 gene mutation, copy number variation (CNV) and DNA sequencing for nucleotide changes followed by prediction of 3D protein model for ligand binding sites. Clinically diagnosed cases of Wilm’s tumour were used for genetic studies using RT-PCR for determine the frequency of gene mutations, CNVs and changes in nucleotide were observed by DNA sequencing (Sanger’s method). Frequency of TGF-βR1 gene mutation was 18.18% observed in WT cases with respect to controls. Similarly, the Tm value (mean) was 90.70 shifted to 91.0 showing significant differences (p=0.24) and C.I. at 95% varying between 2.09-7.09 with copy number variations showing S.D=0.37 and C.I. at 95% 0.337- 0.906. Sequencing data reveals the appearance of two nucleotide sequences TGA→TCA and TGA→CCC, which translates amino acid serine and proline, respectively and consider as “stop codon”. Further mutations were indentified in the form of Insertion/Deletions and 3-D helical structure was predicted for the ligand binding capacity to develop new molecules for cancer therapeutics based on pharmacogenomics.

Background: Conventionally, the dose calculation of intracavitary brachytherapy (ICBT) is carried out using two dimensional (2D) orthogonal x-ray films. In comparison to conventional 2D, three dimensional (3D) image based planning is providing volumetric dose to target and organ at risks (OARs). Due to logistical reasons, it is not feasible to perform 3D image based brachytherapy planning in resource setting radiotherapy centers.

Aim: This study aimed to analyze the dose volume parameters (DVH) for target and OARs in high dose rate (HDR) ICBT treatment planning of carcinoma uterine cervix (Ca-Cx) patients. Our initial experiences of computed tomography (CT) image based ICBT planning.

Materials and Methods: Retrospectively 39 CT image based plans of 13 patients (total 13x3=39 CT) of Ca-Cx were evaluated, who have already treated with Ir-192 HDR brachytherapy. The dose of 7 Gy/fraction for 3 fractions was prescribed and calculated on point ‘A’. The 100% isodoseline of prescribed dose was adjusted using geometrical tools of treatment planning system (TPS) in such a manner that high risk clinical target volume (HR-CTV) was encompassed by at least 90% of isodose line with keeping OARs doses within tolerance limit. The dose volume parameters HR-CTV D₉₀, HR-CTV D₁₀₀ and average point ‘A’ for target and D_2CC for OARs were calculated and evaluated.

Results and Discussion: The combined mean dose for dosimetric parameters HR-CTV D₉₀, HR-CTV D₁₀₀ and average point ‘A’ were found to be 100.82 Gy (S.D.: ± 6.08), 70.95 Gy (S.D.: ± 2.76) and 79.46 Gy (S.D.: ± 0.66) respectively. The combined D_2CC mean dose of bladder, rectum and sigmoid colon were found to be 68.89 Gy (S.D.: ± 8.76), 63.74 Gy (S.D.: ± 3.82) and 73.20 Gy (S.D.: ± 3.04) respectively.

Conclusion: In a resource setting radiotherapy centers 3D-CT image may be used as a moderate option of imaging for ICBT treatment planning of Ca-Cx.

Purpose: Medullary thyroid carcinoma is a rare cancer that arises from parafollicular or C cells which secrete calcitonin. The prognosis is usually poor because, at the time of diagnosis, either lymph node involvement or distant metastases are frequently present and there is no effective treatment for metastatic disease. We report our experience of the first case of solitary bone metastasis of medullary thyroid carcinoma treated with radiofrequency ablation.

Materials and methods: In September 2014 a patient with bone metastasis of medullary thyroid carcinoma was treated with computer tomography guided radiofrequency ablation. The patient was then followed by periodical physical examinations, serum calcitonin levels and Gallium-68 somatostatin receptor positron emission tomography - computed tomography (68Ga PET-CT) until December 2018.

Results: Neither acute nor long-term complications were observed. Local recurrence at the site of the ablated metastasis was not encountered during follow-up, in particular, the patient obtained a partial response using biochemical parameters and a complete response using metabolic parameters.

Conclusion: Radiofrequency ablation could be a new useful treatment modality in bone metastasis of medullary thyroid carcinoma, but further studies are necessary to determine the precise role that this therapy should play in the management of this pathological condition.

Background: The overall survival of patients with pancreatic cancer (PC) is dismal and has improved only slightly during the last decades. Early detection of PC is difficult, and less than 25% of all patients with PC are eligible for surgery. No validated biomarkers exist that identify PC at an early stage and predict treatment outcomes in the individual patient. The objective of the present study is to find diagnostic, prognostic and predictive biomarkers that can be used (1) to diagnose PC with high specificity and sensitivity early in the course of the disease, (2) to improve prognostication, and/or (3) to predict and monitor treatment effectiveness and tolerability for the individual patient.

Methods and analysis: Observational and translational open cohort study with prospective collection of biological materials and clinical data during all stages of the routine care of patients with PC and including patients with suspected pancreatic malignancy disproved after surgery. Blood samples are collected sequentially during the course of a patient’s treatment: before surgery, at start of adjuvant or palliative chemotherapy as well as during treatment until disease progression. The patients are followed until death. Demographics, disease characteristics, comorbidities and lifestyle factors are registered at inclusion and weight and performance status in association with each treatment cycle. Routine blood tests (i.e., haematology, creatinine, liver enzymes, bilirubin, carbohydrate antigen 19-9, C-reactive protein) are collected at regular intervals, and type of operation, chemotherapy and number of cycles given, date of disease recurrence in patients subjected to surgery, date of disease progression for each line of chemotherapy and date of death are recorded. Currently in July 7, 2019 a total of 5156 samples from 2141 patients have been collected.

Discussion: Biomarker analyses include a range of molecules such as deoxyribonucleic acid (DNA), single nucleotide polymorphism (SNPs), ribonucleic acid (RNA), microRNA, proteins and metabolites. Data will be analysed using appropriate methods and statistical analyses.

Conclusion: It is our hope that this ongoing study will provide new information on biomarkers and will contribute to precise treatment options for patients with PC in order to improve outcomes.

Trial Registration: ClinicalTrials.gov ID: NCT03311776. The trial was registered retrospectively; registration date 10/06/2017.