Highlights d Antioxidants stimulate KRAS-driven lung cancer metastasis d Antioxidants reduce free heme levels and stabilize BACH1 d BACH1 activates Hk2 and Gapdh transcription triggering glycolysis-induced metastasis d Targeting BACH1 or its glycolytic targets prevents antioxidant-induced metastasis

Cancer is a class of diseases characterized by uncontrolled cell growth. The current treatment options of cancer are radiotherapy, chemotherapy, hormone therapy, and surgery, where all of them have unpleasant side effects. Due to their adverse side effects, it is challenging to develop new drug for cancer treatment. Hence, the scientists are trying to seek for noble compounds from natural sources to treat cancer. Therefore, in the present investigation, a widely consumable vegetable Basella alba was subjected to evaluate its antiproliferative effect along with molecular signaling of apoptosis in Ehrlich ascites carcinoma (EAC) cell line. Cell growth inhibition was determined by haemocytometer whereas apoptosis of cancer cells were studied by florescence microscope using Hoechst-33342 stain and result was supported by DNA fragmentation and certain cancer related genes expression through PCR analysis. B. alba leaf and seed extract exhibit a considerable scavenging activity in comparison to a standard antioxidant BHT. Moreover, the leaf and seed extracts were able to agglutinate 2% RBC of goat blood at minimum 12.5μg/ml and 50.0μg/ml concentration, respectively. A significant cytotoxic activity was also found in both leaf and seed extract. In haemocytometic observation, the leaf and seed extracts exhibit about 62.54±2.41% and 53.96±2.34% cell growth inhibition, respectively, whereas standard anticancer drug Bleomycin showed 79.43±1.92% growth inhibition. Morphological alteration under fluorescence microscope showed nuclear condensation and fragmentation which is the sign of apoptosis. Apoptosis induction was also confirmed by DNA laddering in leaf and seed treated EAC cells. Upregulation of the tumor suppressor gene P53 and downregulation of antiapoptotic gene Bcl-2 enumerate apoptosis induction. Therefore, current study manifested that leaf and seed extracts of B. alba have antiproliferative activity against EAC cell line and can be a potent source of anticancer agents to treat cancer.

Uveal melanoma (UM) is an intraocular cancer with propensity for liver metastases. The median overall survival (OS) for metastatic UM (MUM) is 1.07 years, with a reported range of 0.84–1.34. In primary UM, high cysteinyl leukotriene receptor 1 (CysLT1) expression associates with poor outcomes. CysLT1 antagonists, quininib and 1,4-dihydroxy quininib, alter cancer hallmarks of primary and metastatic UM cell lines in vitro. Here, the clinical relevance of CysLT receptors and therapeutic potential of quininib analogs is elaborated in UM using preclinical in vivo orthotopic xenograft models and ex vivo patient samples. Immunohistochemical staining of an independent cohort (n = 64) of primary UM patients confirmed high CysLT1 expression significantly associates with death from metastatic disease (p = 0.02; HR 2.28; 95% CI 1.08–4.78), solidifying the disease relevance of CysLT1 in UM. In primary UM samples (n = 11) cultured as ex vivo explants, 1,4-dihydroxy quininib significantly alters the secretion of IL-13, IL-2, and TNF-α. In an orthotopic, cell line-derived xenograft model of MUM, 1,4-dihydroxy quininib administered intraperitoneally at 25 mg/kg significantly decreases ATP5B expression (p = 0.03), a marker of oxidative phosphorylation. In UM, high ATP5F1B is a poor prognostic indicator, whereas low ATP5F1B, in combination with disomy 3, correlates with an absence of metastatic disease in the TCGA-UM dataset. These preclinical data highlight the diagnostic potential of CysLT1 and ATP5F1B in UM, and the therapeutic potential of 1,4-dihydroxy quininib with ATP5F1B as a companion diagnostic to treat MUM.

Cancer is the second death causing disease all over the world and until today 100 different types of cancer have been identified whose treatment methods consist of serious side effects on human body. To reduce the frequency of adverse effects of cancer treatment, nowadays plant derived natural components are getting priority. The plant Morus latifolia is widely available in northern part of Bangladesh. The earlier researches suggested that popular varieties of some Morus sp. like Morus alba, Morus indica etc. have good anti-proliferative activity. Hence, this study was designed to evaluate the anti-proliferative activity of leaf and bark extracts of M. latifolia against Ehrlich's ascites carcinoma (EAC) in vivo. The leaf and bark extracts of M. latifolia were used in several bioassays including Brine shrimp lethality test, hemagglutination activity test, antioxidant activity test, and cell growth inhibition test. Besides, fluorescence microscopy was performed to study apoptotic features in EAC cells, and molecular analysis like real-time PCR were also conducted. The results of Brine shrimp lethality test, hemagglutination activity test, and antioxidant activity assay supported the cell growth inhibition capability of leaf and bark extracts which was confirmed by in vivo cell growth inhibition bioassay. Moreover, the experimental extracts were able to induce cell apoptotis through altering the expression pattern of Bcl-2 and Bax genes. All of the results of this study suggest that several noble compounds are present in M. latifolia plant extracts which are capable for healing cancer cells.

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The clinical significance of the tumor‐immune interaction in breast cancer is now established, and tumor‐infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple‐negative (estrogen receptor, progesterone receptor, and HER2‐negative) breast cancer and HER2‐positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state‐of‐the‐art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false‐positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in‐depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple‐negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

A series of programmed cell death that plays a vital role in the exclusion of abnormal cells without any ruin into the surrounding neighboring cells is called Apoptosis. Generally, it occurs in multi-cellular organisms through an orderly and autonomously processes that is controlled by proper function of various genes. In the current studies, cell apoptosis in EAC cells treated with different fractions (BLP-01, BLP-02 and BLP-03) of leaf extract of B. alba was detected by conducting several bio-assays such as cell growth inhibition, fluorescence and optical microscopy, DNA fragmentation and PCR amplification etc. The results of these experiments indicate that the plant extracts are able to inhibit cell growth significantly where morphological features of apoptosis were appeared under both fluorescence and optical microscope. The PCR amplification results showed that the leaf extracts of B. alba were able to cause EAC cell apoptosis in both the extrinsic and intrinsic pathway. An excellent figure of fragmented DNA was found in DNA fragmentation assay when the gel was observed under UV light which confirms the cell apoptosis. The current findings suggest that the samples of this experiment occupy fascinating competence to conduct cell apoptosis and become an ideal resource for cancer research as well as drugs development for cancer treatment.