A common druggable signature of oncogenic c-Myc, mutant KRAS and mutant p53 reveals functional redundancy and competition among oncogenes in cancer.

The major driver oncogenes MYC, mutant KRAS, and mutant TP53 often coexist and cooperate to promote human neoplasia, which results in anticancer therapeutic opportunities within their downstream molecular programs. However, little research has been conducted on whether redundancy and competition among oncogenes affect their programs and ability to drive neoplasia. By CRISPR‒Cas9-mediated downregulation we evaluated the downstream proteomics and transcriptomics programs of MYC, mutant KRAS, and mutant TP53 in a panel of cell lines with either one or three of these oncogenes activated, in cancers of the lung, colon and pancreas.

Interleukin-6 as a Predictive Factor of Pathological Response to FLOT Regimen Systemic Treatment in Locally Advanced Gastroesophageal Junction or Gastric Cancer Patients.

Background: Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in the Western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy.

Which tumour factors preclude organ preservation in patients with rectal cancer?

Background: cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes, extramural vascular invasion (EMVI) and mesorectal fascia threatening (MRF+) have been utilized as exclusion criteria in several studies on the watch-and-wait (w&w) strategy. Here, our aim was to validate these criteria through a post hoc analysis of two pooled prospective studies on w&w following routine radio(chemo)therapy.

Methods: A review of baseline magnetic resonance imaging was performed in a subgroup of 223 patients treated at a single institution.

To push or to pull? A clinical audit on the efficacy and safety of the pull and push percutaneous endoscopic gastrostomy techniques in oncological patients.

Background: The peroral "pull" technique and the direct "push" procedure are the two main methods for percutaneous endoscopic gastrostomy (PEG) placement. Although pull-PEG is generally recommended as the first-line modality, many oncological patients require a push-PEG approach to prevent tumor seeding or overcome tumor-related obstruction.

Objective: We aimed to compare the efficacy and safety of both PEG procedures in cancer patients.

Association between gene expression signatures and clinical outcomes of pembrolizumab versus paclitaxel in advanced gastric cancer: exploratory analysis from the randomized, controlled, phase III KEYNOTE-061 trial.

Background: In the randomized, controlled, phase III KEYNOTE-061 trial, second-line pembrolizumab did not significantly prolong overall survival (OS) versus paclitaxel in patients with PD-L1-positive (combined positive score ≥1) advanced gastric/gastroesophageal junction (G/GEJ) cancer but did elicit a longer duration of response and offered a favorable safety profile. This prespecified exploratory analysis was conducted to evaluate associations between tumor gene expression signatures and clinical outcomes in the phase III KEYNOTE-061 trial.

Methods: Using RNA sequencing data obtained from formalin-fixed, paraffin-embedded baseline tumor tissue samples, we evaluated the 18-gene T-cell-inflamed gene expression profile (TcellGEP) and 10 non-TcellGEP signatures (angiogenesis, glycolysis, granulocytic myeloid-derived suppressor cell (gMDSC), hypoxia, monocytic MDSC (mMDSC), MYC, proliferation, RAS, stroma/epithelial-to-mesenchymal transition/transforming growth factor-β, WNT).

Safety and efficacy of the FLOT regimen in the Polish population - an analysis of the prospective trial.

As gastric cancer is associated with poor prognosis, the preferred management of locally advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer in European patients is perioperative chemotherapy using the FLOT regimen. Previously published data demonstrate that such treatment is associated with improved disease-free survival (DFS) as well as overall survival (OS) compared to ECF/ECX regimen. In order to collect biomaterial for the identification of serum biomarkers of an early response to neoadjuvant chemotherapy, we performed a prospective study and here, we report the safety and clinical efficacy of this prospective cohort.

The molecular network of the proteasome machinery inhibition response is orchestrated by HSP70, revealing vulnerabilities in cancer cells.

Proteasome machinery is a major proteostasis control system in human cells, actively compensated upon its inhibition. To understand this compensation, we compared global protein landscapes upon the proteasome inhibition with carfilzomib, in normal fibroblasts, cells of multiple myeloma, and cancers of lung, colon, and pancreas. Molecular chaperones, autophagy, and endocytosis-related proteins are the most prominent vulnerabilities in combination with carfilzomib, while targeting of the HSP70 family chaperones HSPA1A/B most specifically sensitizes cancer cells to the proteasome inhibition.

Long-term observation of gastric patients with positive immunocytochemistry of peritoneal washing.

Prognosis in gastric cancer patients is highly dependent on the tumor stage at presentation. Surgery still remains the main therapeutic option in gastric cancer patients. However, the efficacy of this treatment may be substantially limited by the risk of peritoneal dissemination.

Long noncoding RNA CCAT1 rs67085638 SNP contribution to the progression of gastric cancer in a Polish population.

The role of the long noncoding RNA CCAT1 NC_000008.10:g.128220661C > T (rs67085638) in the development of colon cancer has been reported.

GWAS Links New Variant in Long Non-Coding RNA with Colorectal Cancer Susceptibility.

Despite great efforts, most of the genetic factors contributing to the risk of colorectal cancer (CRC) remain undetermined. Including small but homogenous populations in genome-wide association studies (GWAS) can help us discover new common risk variants specific to the studied population. In this study, including 465 CRC patients and 1548 controls, a pooled DNA samples-based GWAS was conducted in search of genetic variants associated with CRC in a Polish population.

Guidelines of the Association of Polish Surgeons and the Polish Society of Surgical Oncology on the accreditation of healthcare centers providing cytoreductive surgery and HIPEC for primary and secondary peritoneal cancers.

Surgical interventions in patients with peritoneal metastases combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and systemic treatment are becoming more common and, when applied to selected patient groups, they reach 5-year survival rates of 32-52%. Good clinical outcomes require experienced and well-equipped healthcare centers, experienced surgical team and adequate patient qualification process. As a result of the discussion on the need for evaluation of quality of care and treatment outcomes and at the request of the Peritoneal Cancer Section of the Polish Society of Surgical Oncology, accreditation standards have been developed and the Accreditation Committee has been established for healthcare centers providing cytoreductive surgery and HIPEC for the management of primary and secondary peritoneal cancers.

The analysis of 3-year adjuvant therapy with imatinib in patients with high-risk molecular profiled gastrointestinal stromal tumors (GIST) treated in routine practice.

Introduction: The real-world data on adjuvant imatinib therapy in high-risk primary GIST are scarce.

Methods: We have analysed the data of 107 consecutive patients with gastrointestinal stromal tumour (GIST) after resection treated with adjuvant imatinib (for planned 3 years with initial dose 400 mg daily, started not later than 4 months after operation) in 6 oncological centres in 2013-2018. All patients were required to have high risk of recurrence (at least 50% according to NCCN/AFIP criteria), known mutational status to exclude PDGFRA D842V mutants and KIT/PDGFRA-wild type cases from therapy without any further selection.

Challenges in Stratifying the Molecular Variability of Patient-Derived Colon Tumor Xenografts.

Colorectal cancer (CRC) is the second most common cancer in Europe and a leading cause of death worldwide. Patient-derived xenograft (PDX) models maintain complex intratumoral biology and heterogeneity and therefore remain the platform of choice for translational drug discovery. In this study, we implanted 37 primary CRC tumors and five CRC cell lines into NU/J mice to develop xenograft models.

Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial.

Background: Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We compared pembrolizumab with paclitaxel in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine.

Methods: This randomised, open-label, phase 3 study was done at 148 medical centres in 30 countries.

The gentamicin-collagen implant and the risk of distant metastases of rectal cancer following short-course radiotherapy and curative resection: the long-term outcomes of a randomized study.

Purpose: A previous randomized study conducted by our group showed that application of gentamicin-collagen implant (GCI) into the pelvic cavity after total mesorectal excision (TME) reduced the incidence of distant metastases. Therefore, we decided to conduct a confirmatory study.

Methods: Patients with rectal cancer were included in the study if they met the following criteria: adenocarcinoma of the rectum, preoperative short-term radiotherapy (5 × 5 Gy), and WHO performance score 0-1.

Conventional cytology vs. immunocytochemistry of intraoperative peritoneal washes in gastric cancer patients subjected to gastrectomy: clinical correlates and association with overall survival.

Background: The aim of this study was to verify if positive results yielded with conventional cytology and immunocytochemical analysis of peritoneal washes correlate with established prognostic factors and overall survival (OS) in gastric cancer patients.

Methods: The study included the data of 271 gastrectomized patients. Peritoneal washes of 131 (48.

Cytoreductive surgery and HIPEC in the treatment of peritoneal metastases of sarcomas and other rare malignancies.

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The safety of low-molecular-weight heparins in the prevention of venous thromboembolism in surgically-treated cancer patients: results of a multicentre observational study.

Aim Of The Study: Despite widespread use of pharmacological prophylaxis, venous thromboembolism (VTE) still constitutes a common complication in cancer patients. The aim of the study was to analyse the safety of low-molecular-weight heparins (LMWH) in the prevention of VTE in surgically-treated cancer patients.

Material And Methods: A total of 5207 cancer patients (44.

The risk of anastomotic leakage after anterior resection: retrospective analysis of 501 rectal cancer patients operated without protective stoma.

Background: The aim of this study was to verify the accuracy of the existing scoring system for the assessment of anastomotic leakage risk after anterior resection and to identify additional risk factors that were not included in this classification.

Methods: The study included 501 consecutive rectal cancer patients who underwent anterior resection without formation of protective stoma. The risk for anastomotic leakage was determined using a previously proposed scoring system based on three factors: male sex, intraoperative blood loss and level of anastomosis.

Preservation of duodenal passage as a determinant of short- and long-term quality of life in gastric cancer patients after total gastrectomy.

Background: The aim of this prospective study was to compare subjective and objective quality of life (QoL) of gastric cancer patients after total gastrectomy with and without preservation of the duodenal passage during short- and long-term follow-up.

Methods: The study included 68 patients, among them 37 (54%) persons subjected to total gastrectomy with Roux-Y reconstruction (R-Y group) and 31 (46%) individuals in whom gastrectomy was followed by formation of Henley-Longmire loop (H-L group). Subjective and objective QoL was determined 1 and 10 years postsurgery.

Evaluation of miR-506 and miR-4316 expression in early and non-invasive diagnosis of colorectal cancer.

Purpose: Examination of the entire colon by colonoscopy remains the golden standard for screening of colorectal cancer (CRC). However, patients are reluctant to perform invasive colonoscopies because of interference with their intimacy. Therefore, the potential use of non-invasive analysis of microRNAs expression in liquid biopsy as a novel biomarker for early CRC has investigated in several studies.