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Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide in both sexes. Current therapies include surgery, chemotherapy, and targeted therapy; however, prolonged exposure to chemical agents induces toxicity in patients and drug resistance. So, we implemented a therapeutic strategy based on the combination of doxorubicin, metformin, and sodium oxamate called triple therapy (Tt). We found that Tt significantly reduced proliferation by inhibiting the mTOR/AKT pathway and promoted apoptosis and autophagy in CRC derived cells compared with doxorubicin. Several autophagy genes were assessed by western blot; ULK1, ATG4, and LC3 II were overexpressed by Tt. Interestingly, ULK1 was the only one autophagy-related protein gradually overexpressed during Tt administration. Thus, we assumed that there was a post-transcriptional mechanism mediating by microRNAs that regulate UKL1 expression during autophagy activation. Through bioinformatics approaches, we ascertained that ULK1 could be targeted by mir-26a, which is overexpressed in advanced stages of CRC. In vitro experiments revealed that overexpression of mir-26a decreased significantly ULK1, mRNA, and protein expression. Contrariwise, the Tt recovered ULK1 expression by mir-26a decrease. Due to triple therapy repressed mir-26a expression, we hypothesized this drug combination could be involved in mir-26a transcription regulation. Consequently, we analyzed the mir-26a promoter sequence and found two HIF-1α transcription factor recognition sites. We developed two different HIF-1α stabilization models. Both showed mir-26a overexpression and ULK1 reduction in hypoxic conditions. Immunoprecipitation experiments were performed and HIF-1α enrichment was observed in mir-26a promoter. Surprisingly, Tt diminished HIF-1α detection and restored ULK1 mRNA expression. These results reveal an important regulation mechanism controlled by the signaling that activates HIF-1α and that in turn regulates mir-26a transcription.

Introduction: Acrometastasis is infrequent and generally indicates a wider spread of metastasis with poor prognosis. The diagnosis is challenging, as it might mimic an infectious, inflammatory, or metabolic disease. Acrometastasis are most commonly found in patients with lung, gastrointestinal, kidney, and breast cancer. Only 3 cases of cervical cancer associated with hand metastasis have been reported in the literature. Patient concerns: Herein, we report a 58-year-old patient with locally advanced cervical cancer and recurrence in the right thumb as presentation of widespread disseminated disease. She initially presented with adenocarcinoma of the uterine cervix and was treated with concurrent chemoradiation followed by high-dose rate brachytherapy. Six months later, she developed an insidious onset of pain and swelling in the right thumb, erythema, and edema, mimicking cellulitis. Diagnosis: A biopsy of the soft tissues of the thumb was performed, and the histopathology indicated metastasis of adenocarcinoma to the bone and soft tissues. Interventions and outcomes: The patient rejected further treatment and died of progressive disease 4 months after the diagnosis of the recurrence. Conclusion: Metastases in unusual sites are a diagnostic challenge, and there is no standardized treatment. Timely diagnosis and treatment can improve the prognosis of these patients and might preserve their quality of life.

Background Even with different histologic origins, squamous cell carcinoma (SCC) and adenocarcinoma (AC) are considered a single entity, and the first-line treatment is the same. Locally advanced disease at the diagnosis of cervical cancer is the most important prognostic factor, the recurrence rate is high, making it necessary to evaluate prognostic factors other than clinical or radiological staging; histology could be one of them but continues to be controversial. The aim of this study was to evaluate tumor histology as a prognostic factor in terms of treatment outcomes, disease-free survival (DFS) and overall survival (OS) in a retrospective cohort of patients with Locally Advanced Cervical Carcinoma (LACC). Methods The records of 1291patients with LACC were reviewed, all of them were treated with 45–50 Gy of external beam radiotherapy with concurrent chemotherapy and brachytherapy. A descriptive and comparative analysis was conducted. Treatment response was analyzed by the chi-square test; DFS and OS were calculated for each histology with the Kaplan–Meier method and compared with the log-rank test; and the Cox model was applied for the multivariate analysis. Results We included 1291 patients with LACC treated from 2005 to 2014, of which 1154 (89·4%) had SCC and 137 (10·6%) had AC. Complete response to treatment was achieved in 933 (80·8%) patients with SCC and 113 (82·5%) patients with AC. Recurrence of the disease was reported in 29·9% of SCC patients and 31·9% of AC patients. Five-year DFS was 70% for SCC and 62·2% for AC. The five-year OS rates were 74·3% and 60% for SCC and AC, respectively. The mean DFS was 48·8 months for SCC vs 46·10 for AC (p = 0·043), the mean OS was 50·8 for SCC and 47·0 for AC (p = 0·002). Conclusion Our findings support the hypothesis that SCC and AC are different clinical entities. Trial Registration NCT04537273.