MALSU1-mediated regulation of mitochondrial function governs proliferation and doxorubicin resistance in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) poses a formidable challenge in oncology due to its aggressive nature and limited treatment options. Although doxorubicin, a widely used chemotherapeutic agent, shows efficacy in TNBC treatment, acquired resistance remains a significant obstacle. Our study explores the role of MALSU1, a regulator of mitochondrial translation, in TNBC and its impact on cell proliferation and doxorubicin resistance. We observed increased MALSU1 expression in TNBC, correlating with poor patient prognosis. MALSU1 knockdown in TNBC cells significantly reduced proliferation, indicating its pivotal role in sustaining cell growth. Mechanistically, MALSU1 depletion resulted in decreased activities of mitochondrial respiratory chain complexes, cellular ATP levels, and mitochondrial respiration. Notably, exogenous addition of normal mitochondria restored proliferation and mitochondrial respiration in MALSU1-depleted TNBC cells. Importantly, MALSU1 knockdown enhanced the sensitivity of doxorubicin-resistant TNBC cells to doxorubicin treatment. Furthermore, pharmacological inhibition of mitochondrial translation using tigecycline and chloramphenicol mimicked the effects of MALSU1 knockdown, suggesting mitochondrial translation as a potential therapeutic target. Taken together, our findings not only elucidate the intricate role of MALSU1 in TNBC biology and doxorubicin resistance but also lay the groundwork for future investigations targeting MALSU1 and/or mitochondrial translation as a promising avenue for developing innovative therapeutic strategies against TNBC.

PYCR3 modulates mtDNA copy number to drive proliferation and doxorubicin resistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) poses significant challenges in treatment due to its aggressive nature and limited therapeutic targets. Understanding the underlying molecular mechanisms driving TNBC progression and chemotherapy resistance is imperative for developing effective therapeutic strategies. Thus, in this study, we aimed to elucidate the role of pyrroline-5-carboxylate reductase 3 (PYCR3) in TNBC pathogenesis and therapeutic response. We observed that PYCR3 is significantly upregulated in TNBC specimens compared to normal breast tissues, correlating with a poorer prognosis in TNBC patients. Knockdown of PYCR3 not only suppresses TNBC cell proliferation but also reverses acquired resistance of TNBC cells to doxorubicin, a commonly used chemotherapeutic agent. Mechanistically, we identified the mitochondrial localization of PYCR3 in TNBC cells and demonstrated its impact on TNBC cell proliferation and sensitivity to doxorubicin through the regulation of mtDNA copy number and mitochondrial respiration. Importantly, Selective reduction of mtDNA copy number using the mtDNA replication inhibitor 2', 3'-dideoxycytidine effectively recapitulates the phenotypic effects observed in PYCR3 knockout, resulting in decreased TNBC cell proliferation and the reversal of doxorubicin resistance through apoptosis induction. Thus, our study underscores the clinical relevance of PYCR3 and highlight its potential as a therapeutic target in TNBC management. By elucidating the functional significance of PYCR3 in TNBC, our findings contribute to a deeper understanding of TNBC biology and provide a foundation for developing novel therapeutic strategies aimed at improving patient outcomes.

Clinical Efficacy, Survival, and Adverse Reaction Evaluation of Immune Checkpoint Inhibitor in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.

Objective: To systematically assess the clinical effect and survival time of immune checkpoint inhibitor (ICIs) in advanced gastric cancer (GC) and adverse reactions to provide evidence-based medicine for its enhancement and adoption. Methods: PubMed, EMBASE, ScienceDirect, Cochrane Library, China Knowledge Network database (CNKI), China VIP database, Wanfang database, and China Biomedical Literature Database (CBM) online database were searched for randomized controlled trials (RCT) of immuno-checkpoint inhibitors in advanced GC therapy. Retrieval time was limited to the period from the date the database was established to present. Separately, two researchers gathered the data. Statistical software RevMan5.4 was used to estimate bias risk according to the Cochrane Handbook 5.3 standard. Results: The computer database retrieved 1723 articles, and 465 articles were eliminated when repeated studies were removed. After screening the titles and abstracts of 287 articles, 124 articles were contained after eliminating irrelevant studies, reviews, case reports, and no control literature. After carefully reading 108 studies with insufficient data and no major outcome markers, 6 RCTs were eventually contained. 4 articles compared the levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) after treatment. The result indicated that the levels of serum CEA and CA199 in the study group were notably lower, and the difference was statistically significant (P < 0.05). The immune function indexes after treatment were compared, suggesting that the improvement of immune function indexes in the study group was notably better, and the difference was statistically significant (P < 0.05). Three clinical trials reported the median progression-free survival (PFS). The PFS of the study group was notably longer after treatment, and the difference was statistically significant (P < 0.05). The occurrence of adverse reactions after treatment was analyzed by meat, and all the literatures were analyzed. No notable differences were observed in the incidence of adverse reactions. Conclusion: ICIs associated with chemotherapy is effective when treating GC, which can effectively promote the disease control rate of patients, enhance immune function, reduce the level of tumor markers, and prolong survival time. The safety is controllable, which is worth popularizing in clinical practice. However, more studies and follow-up with higher methodological quality and longer intervention time are needed to further verify it.

Changes of Intestinal Flora and Its Relationship with Nutritional Status for Patients with Cancer Pain.

Objective: To study the changes in the intestinal flora and its relationship with nutritional status for patients with cancer pain. Methods: A prospective research method was adopted. One hundred twenty cancer patients with cancer pain were selected as the research objects, who were treated in our hospital from June 2019 to June 2020, and 120 cancer patients without cancer pain were selected as the control group, who were treated in the same period. The differences of the intestinal flora and nutritional status of patients with different severity between the observation group and the control group were compared to analyze the changes of intestinal flora in patients with cancer pain and its correlation with nutritional status. Results: Hemoglobin (HB) (t = 17.141, p ≤ 0.001), albumin (ALB) (t = 27.654, p ≤ 0.001), prealbumin (PAB) (t = 96.192, p ≤ 0.001), and total protein (TP) (t = 18.781, p ≤ 0.001) in the observation group were significantly lower than those in the control group. There were statistically significant differences in HB (f = 13.569, p ≤ 0.001), ALB (f = 22.229, p ≤ 0.001), PAB (f = 19.521, p ≤ 0.001), and TP (f = 21.451, p ≤ 0.001) among patients with cancer pain of different severity. Through these two comparisons, their nutritional indicators showed a significant downward trend with the increase in the severity for cancer pain patients; the levels of Lactobacillus (t = 2.124, p = 0.035), Bifidobacterium (t = 4.823, p ≤ 0.001), Enterococcus (t = 3.578, p ≤ 0.001), and Eubacterium (t = 2.394, p = 0.017) in the observation group were significantly lower than those in the control group. There were statistically significant differences in the levels of Lactobacillus (f = 20.643, p ≤ 0.001), Bifidobacterium (f = 19.129, p ≤ 0.001), Enterococcus (f = 17.408, p ≤ 0.001), and Eubacterium (f = 22.343, p ≤ 0.001) among patients with cancer pain of different severity. After pairwise comparison, their beneficial intestinal bacteria were significantly lower than those in the control group with the increase in pain in cancer pain patients. Nitric oxide (NO) (t = 8.418, p ≤ 0.001), galectin-3 (t = 14.043, p ≤ 0.001), occludin (OCLN) (t = 47.308, p ≤ 0.001), galectin-1 (t = 15.298, p ≤ 0.001), zonula occludens protein 1 (ZO-1) (t = 23.093, p ≤ 0.001), and cingulin (t = 340.198, p ≤ 0.001) in the observation group were significantly lower than those in the control group. There were statistically significant differences in NO, galectin-3, OCLN, galectin-1, ZO-1, and cingulin for patients with cancer pain of different severity. By comparison, the NO, galectin-3, OCLN, galectin-1, ZO-1, and cingulin of the patients showed a significant downward trend with the aggravation of cancer pain symptoms. Through correlation analysis, the nutritional indicators of patients were positively correlated with intestinal microorganisms and intestinal barrier function. Conclusion: There was a significant correlation between the changes in intestinal flora and nutritional status for patients with cancer pain, which could be used as an important basis for improving the treatment of cancer pain.

High-dose OxyContin to treat pain associated with bone metastasis in patients with small-cell lung cancer: a case study report.

Pain management is an important topic that has received extensive attention from clinical practitioners. Nearly all patients with malignant tumors suffer pain at the advanced stage of their disease. Oxycodone is a first-line choice for treating moderate-to-severe cancer-related pain, and OxyContin, a controlled-release oxycodone hydrochloride tablet, is internationally recognized as a safe and effective opioid analgesic. OxyContin has the characteristics of both immediate release and sustained release, with a time to onset and peak similar to those of immediate-release morphine. It acts on both µ and κ receptors and has been shown to be effective in treating different types of pain, especially neuropathic pain, theoretically without a dose cap. However, the dose is limited in clinical applications due to various factors that are likely to affect its analgesic effect and reduce patient quality of life. Cooperation with a patient's family members is required during the treatment of cancer pain. Chronic cancer pain has a long disease course, which could easily cause complex psychological symptoms due to their important role in the pain experience. Pain is controllable, and patients have a right to not experience pain. An optimal living state can be achieved through collaboration between physicians and patients. Rational personalized treatment of cancer pain can improve patient quality of life, relieve pain, and help prolong patient survival. This article reports the treatment procedure and adverse reactions in a patient who was treated with high-dose OxyContin, with the aim of providing a reference for other clinical practitioners.