araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Signaling Pathways Targeting Colorectal Cancer in Egypt

Summary: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related death worldwide. In Egypt, CRC constitutes 4.2% of all cancers with median age is 50 years old.

Detailed description: The TP53-induced glycolysis and apoptosis regulator (TIGAR) is a transcriptional target of p53. TIGAR functions as a fructose-2,6-bisphosphatase, decreasing the flux through the main glycolytic pathway. Consequently, glucose metabolism diverted into the pentose phosphate pathway (PPP). This results in TIGAR-mediated increase in cellular NADPH production, which contributes to the scavenging of ROS by reduced glutathione and thus a lower sensitivity of cells to oxidative stress-associated apoptosis. PPP also produce ribose phosphate for DNA synthesis and repair that play a role in tumor development and cell survival in tumor microenvironment. A high expression level of TIGAR was observed in cancers such as breast cancer, hepatocellular carcinoma, intestinal cancer, and glioblastoma. These studies suggested that TIGAR may act as an oncogene that support cancer progression.
  The tripartite motif containing 59 (TRIM) proteins have been implicated in many biological processes including cell differentiation, apoptosis, transcriptional regulation, and signaling pathways.
  It is related to several cancers. The oncogenic effect of TRIM59 on tumor proliferation and migration has been studied in various cancers, including gastric cancer, osteosarcoma, lung and CRC. The biological activity of TRIM59 has been observed to be closely associated with the regulation of P53. TRIM59 interacts with P53, leading to P53 ubiquitination and degradation, and consequently promotes tumor growth and migration. TRIM59 functions as an oncogene in CRC progression. It also activates the PI3K/AKT pathway. Increased activity of this pathway is often associated with tumor progression and resistance to cancer therapies. AKT can control TIGAR protein translation by activation of mTOR.
  Targeting TRIM59 inhibition will inhibit PI3K-Akt pathway downregulate TIGAR protein translation. This is in turn downregulates GSH levels, increases ROS production, leading to cell death and blocks the cellular proliferation and survival of cancer cells leading to tumor regression. Therefore, TRIM59 protein can serve as a new potential therapeutic target for CRC.

Eligibility: Inclusion Criteria:
  -  All Patients confirmed histopathologically to have early stages of colorectal cancer.
  -  Risky group patients (including those with ulcerative colitis, chron's disease, familial adenomatous polyposis).
  Exclusion Criteria:
  -  Patients with previous history of CRC treated with chemotherapy or presence of other types of cancer.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Efficacy and Safety in Patients With Chronic Lymphocytic Leukemia (CLL) Treated With Idelalisib and Rituximab in the Clinical Practice: a GIMEMA-ERIC Study

Summary: The present study aims at obtaining more in-depth information on how patients with chronic lymphocytic leukemia treated with idelalisib and rituximab react to treatment.

Detailed description: This cohort study will recruit patients with treatment-naïve chronic lymphocytic leukemia (CLL) with TP53 disruption (i.e. 17p- or TP53 mutations) or relapsed/refractory CLL who were treated with idelalisib and rituximab between 01/07/2014 and 31/05/2017 at European centres adhering to the GIMEMA group and the ERIC group.

Eligibility: Inclusion Criteria:
  -  Diagnosis of CLL / Small Lymphocytic Lymphoma (CLL/SLL) according to the World Health Organisation (WHO) classification 2008.
  -  Treatment with idelalisib and rituximab started between the date of Country marketing authorization approval of idelalisib (EMA approval 18/09/2014) and 31/05/2017 given at European centres adhering to the GIMEMA group and the ERIC group.
  -  One of the two following conditions must be satisfied:
  -  Previously untreated CLL requiring therapy according to the NCI criteria (Hallek M et al, Blood 2008)] with deletion 17p13 and/or TP53 mutation.
  -  Relapsed refractory CLL., i.e. patients who received at least one previous line of treatment using alkylating agents and/or purine analogues with or without monoclonal antibodies, or high dose steroids requiring therapy according to the NCI criteria (Hallek M et al, Blood 2008)
  -  Age ≥ 18 years.
  -  Signed written informed consent, if applicable, according to ICH/EU/GCP and national local law.
  Exclusion Criteria:
  -  Patients with CLL treated with idelalisib within interventional clinical trials or outside the approved indication.
  -  Patients with:
  -  Transformation of CLL to aggressive lymphomas (Richter's Syndrome).
  -  HIV infection.
  -  Active and uncontrolled HCV and/or HBV infections or liver cirrhosis.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Blood Markers of Early Pancreas Cancer

Summary: Identifying biomarkers of early pancreatic ductal adenocarcinoma (PDAC) could facilitate screening for individuals at higher than average risk and expedite the diagnosis in individuals with symptoms and substantially improve an individual's chance of surviving the disease.
  The investigators propose a longitudinal study of subjects at higher than average risk of PDAC in order to generate clinical data and bank serial blood specimens.

Detailed description: Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) have only an 8% chance of surviving 5 years after diagnosis. Most PDAC is advanced and not amenable to curative therapies at the time of diagnosis, owing to lack of symptoms in early disease, nonspecific symptoms when they do develop resulting in a delay in diagnosis. Identifying biomarkers of early PDAC could facilitate screening for individuals at higher than average risk and expedite the diagnosis in individuals with symptoms and substantially improve an individual's chance of surviving the disease.
  The investigators propose a longitudinal study of subjects at higher than average risk of PDAC in order to generate clinical data and bank serial blood specimens. Subjects will include individuals with family history of pancreas cancer, individuals with cystic pancreas lesions or chronic pancreatitis, and individuals with new-onset diabetes. Identifying specific biomarkers - blood markers and/or a clinical "prodrome" - in participants who go on to develop PDAC could improve the diagnostic approach outcomes for patients diagnosed with PDAC.

Eligibility: Inclusion Criteria:
  General inclusion criteria:
  1. Age ≥19
  2. Able to provide written, informed consent
  Exclusion Criteria:
  General exclusion criteria:
  1. Personal history of PDAC
  2. Currently receiving treatment for a cancer diagnosis (excluding long-term hormonal therapy)
  3. Pre-diabetes on metformin for ≥ 3 years

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: A Biospecimen Collection Study in BRAF-V600E Mutated Recurrent Gliomas

Summary: This is a surgical biospecimen collection study. The purpose of this study is to understand how much of two drugs (dabrafenib and trametinib) are able to penetrate brain tumors and turn off the RAF signaling pathway. This is important because these drugs are currently FDA approved for other tumors and may have efficacy in brain tumors with the BRAF V600E mutation.

Detailed description: The primary goal of this study is to establish concentrations of dabrafenib and trametinib in enhancing brain tissue and cerebrospinal fluid from people with BRAF-V600E mutant recurrent gliomas who undergo tumor resection. The exploratory goals are to measure the amount of ERK signaling pathway activity, to identify mechanisms of resistance to these drugs, and evaluate feasibility of measuring tumor DNA in cerebrospinal fluid.
  People (adults or children) with brain tumors who are already taking dabrafenib and / or trametinib and are in need of a surgical resection are potentially eligible. On the day of surgery, blood, cerebrospinal fluid, and tumor tissue will be collected for research purposes.

Eligibility: Inclusion Criteria:
  -  Subjects must have a history of primary brain tumor (including but not limited to glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic ganglioglioma (AG), and anaplastic pleomorphic xanthoastrocytoma (PXA)).
  -  Subjects must have a BRAF-V600 mutation identified in previous tissue analysis (may be IHC or PCR based). Allowable mutations include V600E, V600K, V600R, and V600D.
  -  Subjects must be taking dabrafenib at a dose of at least 50mg twice daily (adults only) and / or trametinib at a dose of at least 1mg daily (adults only) for at least 7 days prior to surgery as prescribed by their treating physician. Note: Pediatric patients may be taking any dose of dabrafenib and / or trametinib as prescribed by their treating physician for at least 7 days prior to surgery.
  -  Subjects must be undergoing surgery for clinical purposes.
  -  Written informed consent - a signed informed consent and/or assent (as age appropriate) for study participation will be obtained according to institutional guidelines.
  Exclusion Criteria:
  -  Subjects who are receiving any other investigational agents or chemotherapeutic agents.
  -  Subjects for whom collection of blood, spinal fluid, or tissue samples is unsafe or clinically inadvisable.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Evaluation of Early Relapse After Mandibular Lengthening Surgery

Summary: The goal of this study is to evaluate whether the use of a bone graft substitute at the osteotomy site will result in better stability and diminish early relapse after mandibular lengthening surgery.
  The study focuses on the evaluation of the following hypothesis:
  The use of bone graft substitute at the osteotomy site has an influence on:
  -  The 3-dimensional stability of the osteotomy site
  -  Early relapse based in the plasticity of the site

Detailed description: Bilateral sagittal split osteotomy (BSSO)of the mandible is a surgical procedure used to correct dentofacial discrepancies. Post-operative stability is of great concern for CMF (Cranio maxillo facial) surgeons as the goal is to achieve optimal functional outcomes, good aesthetic results and satisfaction of patients' concerns. Skeletal relapse is a known complication of mandibular lengthening surgery and is divided into two groups; short term or early relapse and long term or late relapse.
  Short term relapse occurs within the first 6 to 8 weeks post-operatively and is due to intersegmental movement at the osteotomy site (osteotomy slippage) and osteosynthesis slippage. Late relapse is thought to be caused by progressive condylar resorption, a clinical entity affecting the temporomandibular joint.
  The rationale to reconstruct the lateral cortical defect resulting from mandibular advancement with BSSO with a bone graft substitute lies in the prevention of an unaesthetic notching at the inferior border. The use of a self-hardening, space-occupying paste could add mechanical stability, thus increase 3D-stability at the osteotomy site and prevent early relapse.
  The use of cone-beam computed tomography (CBCT) in the treatment planning and postoperative follow-up of orthognathic patients has provided the surgeons with a new three-dimensional imaging modality to evaluate the postoperative skeletal relapse and postoperative morphologic changes of the condyles. Skeletal relapse, as well as positional and dimensional changes of the condyles, can be quantified in three dimensions.

Eligibility: Inclusion Criteria:
  -  Class II occlusion of non-syndromic origin, mandibular hypoplasia
  -  Availability of pre- and postoperative CBCT scans of sufficient quality
  -  Age: >10years
  Exclusion Criteria:
  -  Previous orthognathic surgical treatment
  -  Simultaneously performed genioplasty
  -  Plate osteosynthesis
  -  Buccal plate fracture during surgery

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Offspring Born to Mothers With Polycystic Ovary Syndrome in Guangzhou Cohort Study

Summary: The Offspring Born to Mothers with Polycystic Ovary Syndrome in Guangzhou Cohort study (PCOS-BIG) was established to investigate the short- and long-term effects of intrauterine exposure to maternal PCOS on the health of offspring in Guangzhou, China. Data are collected regarding maternal PCOS subtypes, nursing, diet and education as well as health outcomes in their later life. Biological samples including blood and tissue samples are also collected from participants.

Detailed description: According to preliminary survey, the prevalence of polycystic ovary syndrome (PCOS) among Chinese women reached 7.5%. Hyperandrogenism and insulin resistance were considered as the main pathogenesis of PCOS. As reported, the secretion of androgen is higher among women with PCOS than the healthy reference population throughout their fertile lives. Worth of concern, offspring of PCOS patients presented with glucolipid metabolism disorders as early as during their childhood, while whose pathogenesis remains unclear. Prenatal exposure of rhesus monkey in pregnant to androgens produces glucolipid metabolic alterations in offspring resembling those in PCOS, suggesting that the exposure of the fetus to hyperandrogenism during gestation could affect the glucolipid metabolism of PCOS offspring. Growing evidence shows that different exposures during pregnancy will affect the DNA methylation of offspring and disturb their endocrine and metabolism. A birth cohort would provide an opportunity to examine the short- and long-term effects of PCOS exposure, such as hyperandrogenism, on health consequences of the offspring.

Eligibility: Inclusion Criteria:
  -  Offspring born to women diagnosed with PCOS
  -  Offspring born to women with <20 weeks of gestation, intended to eventually deliver in Guangzhou Women and Children's Medical Center
  -  Permanent residents or families intended to remain in Guangzhou for ≥3 years
  Exclusion Criteria:
  -  None

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: The Influence of BMI on Core Stability in Healthy Adults

Summary: This study will be conducted to investigate the influence of body mass index (BMI) on core stability (CS) in healthy subjects. The participants in this study will be 90 healthy subjects with right dominant lower limb (49 females and 49 males) they will be recruited from College of Applied Medical Sciences, Jazan University.

Detailed description: Subjects will be categorized according to BMI into three groups:
  Group I (normal subjects): 30 individuals (15 male, and 15 female students) with (BMI<25 kg//m^2)) Group II (overweight subjects): 30 individuals (15 male, and 15 female students) with (BMI, 25-30 kg//m^2)).
  Group III (obese subjects): 30 individuals (15 male, and 15 female students) (BMI>30 kg//m^2)).
  Motor control element of CS will be investigated by assessing bilateral static balance with open and close eye, right foot balance test, and dynamic balance test using Prokin System for balance. Data of this study will be statistically analyzed by performing descriptive (Mean and standard deviation) and inferential statistics (One way ANOVA, Unpaired T test) at level of significance p=<0.05.

Eligibility: Inclusion Criteria:
  1. Subjects would not have any diseases of the central nervous system.
  2. Subjects would not have any orthopedic disorders either of the trunk or the lower limbs in the previous year.
  3. None of the subjects has history of balance training ( Erkmen et al., 2010, Li Li, 2012) .
  Exclusion Criteria:
  1. Sign of foot pain, reduced tactile and thermal foot sensibility.
  2. Peripheral neuropathy.
  3. A history of previous back or abdominal surgery/injury
  4. A history of patellofemoral pain syndrome, plantar fasciitis, and back pain .
  5. Limb-length discrepancy, and anterior or posterior tibialis dysfunction.
  6. Evidence of a systemic or musculoskeletal disease within the past six months (AlAbdulwahab & Kachanathu, 2016).

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Prophylactic Donor Lymphocyte Infusion After Allo-PBSCT for Patients With Very High-risk Hematologic Malignancies

Summary: Unmanipulated allogenic peripheral blood stem cell transplantation (allo-PBSCT) has been an established treatment to cure high-risk leukemia/lymphoma. Relapse is the main cause of treatment failure for patients with relapsed/refractory disease or with very high-risk gene mutations such as TP53, TET2 and DNMT3a. Donor lymphocyte infusion (DLI) is an option to reduce relapse after allo-PBSCT for very high-risk disease without effective targeted therapy. In this study, the investigators aimed to compare the safety and efficacy of prophylactic DLI with G-CSF-primed peripheral blood progenitors for prevention of relapse after allo-PBSCT in patients with very high-risk leukemia/lymphoma.

Detailed description: Conventional DLI has invariably been associated with high rates of severe graft-versus-host disease (GVHD) and GVHD-related non-relapse mortality (NRM). Thus, in our previous studies, the DLI procedure has been modified to use G-CSF-mobilized peripheral blood stem cells (PBSCs) instead of steady-state lymphocytes. G-CSF mobilization results in the modulation of the polarization potential of T cells from Th1 to Th2. In addition, T-cell hyporesponsiveness is induced via the proliferation of dendritic cell 2 and monocytes and the down-regulation of CD28/B7. Furthermore, G-CSF augments NK-T-cell-dependent CD8+ cytotoxicity. These data constructed the rationale for the use of G-CSF-primed peripheral blood DLI to reduce DLI-associated GVHD and enhance the GVT effect of DLI. To date, there is no effective target therapy for acute leukemia with gene mutations such as DNMT3A, TET2 and TP53 and their response to chemotherapy and survival even after allogenic stem cell transplantation remains poor. Hypomethylating agents were reported to reverse the repression of HLA molecules and cancer testis antigens on leukemia cells, rendering them more sensitive to anti-leukemic activity mediated by DLI. The use of low-dose decitabine after allogenic stem cell transplantation was safe for early hematopoietic reconstitution. Therefore, decitabine was planned to be given prior to prophylactic DLI in the current study.

Eligibility: Inclusion Criteria:
  -  disease in the non-remission (NR) state prior to transplantation, including primary induction failure, relapse untreated or refractory to reinduction chemotherapy.
  -  achieving CR1 with ≥3 cycles of induction of chemotherapy.
  -  carrying TP53, DNMT3a, TET2 or FLT3-ITD gene mutation.
  Exclusion Criteria:
  -  early relapse, either molecular relapse or hematological relapse.
  -  primary or secondary graft failure.
  -  concomitant uncontrolled disease and/or organ dysfunction (infection, severe heart, renal, respiratory or hepatic failure…).

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Study of Accurate Diagnosis and Treatment of Peutz-Jeghers Syndrome

Summary: The mutation of STK11 has been regcognized to be the major cause of Peutz-Jeghers syndrome (PJS).The aim of this study was to confirm the mutation rate of gene associated with gastrointestinal malignancies,including STK11, APC,PMS1,et al. Furtherly, the investigators analyze the association of STK11 with gut microbiota.

Detailed description: All patients diagnosed as PJS were enrolled and accepted second generation gene sequencing with their blood specimens. Then all patients allocated into gene mutation group and no gene mutation group according to if the cases accompany with gene mutation of STK11.Also, health persons were enrolled and a case controlled study will be carried out.All patients and health persons accepted 16s rRNA sequencing with their feces specimens.

Eligibility: Inclusion Criteria:
  1. Subject with ages from 18-70 years old.
  2. Subject diagnosed with Peutz-Jeughers syndrome.
  3. Subject without hypertension, diabetes and other gastrointestinal diseases.
  4. The consent form has been signed.
  Exclusion Criteria:
  1. Subject is younger than 18 years or older than 70 years.
  2. Subject with hypertension,diabetes and other gastrointestinal diseases.
  3. Subject taken or adminstered medicine associated with digestive function during latest 1 month.
  4. Pregnant women.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Post-marketing Registration Study of Nifekalant Hydrochloride (NIF) Injection

Summary: Retrospective and Prospective single arm, observational study to evaluate efficacy and safety of NIF in the treatment of ventricular tachycardia and ventricular fibrillation. The information registration of the target population will be collected with the hospital HIS system or LIS system.

Detailed description: Subjects enrolled in the retrospective study may be enrolled in a prospective study if the study drug is re-used, but in the end only the most-registered case of the subject would be collected.
  The recommended treatment plan for this study is from the usage and dosage of NIF. The clinician can make appropriate adjustments to the specific usage and dosage according to the patient's condition.
  Load dose: Adults usually use 0.3mg/kg each time, under continuous ECG monitoring, the injection should be completed within 5 minutes, and the maximum dose should not exceed 0.5 mg/kg.
  Maintenance dose: After load injection, the adult routine dose is 0.4 mg/kg/h under continuous ECG monitoring. The dosage could be appropriately increased or decreased according to the patient's reaction, but the maximum dose should not exceed 0.8 mg/kg/h.

Eligibility: Inclusion Criteria:
  -  Patients with life-threatening ventricular tachycardia or ventricular fibrillation in cases where other drugs are ineffective or inoperable.
  -  Patients who have received or are about to receive Nifekalant Hydrochloride for treatment according to the instructions.
  Exclusion Criteria:
  -

Relevance to patient case: not relevant