Background Despite the progress of advanced target therapeutic agents and immune checkpoint inhibitors, EGFR‐TKI resistance is still one of the biggest obstacles in treating lung cancer. Clinical studies with autophagy inhibitors are actively underway to overcome drug resistance. Methods We used PC9, PC9/GR, and HCC827/GR cell lines to evaluate the activation of autophagy and EGFR‐TKI resistance. Chloroquine was applied as an autophagic blocker and verteporfin was utilized as a YAP inhibitor. Results In this study, we tried to reveal the effect of autophagy adaptor p62 which is accumulated by autophagy inhibitor in EGFR‐TKI‐resistant lung adenocarcinoma. We identified that p62 has oncogenic functions that induce cell proliferation and invasion of EGFR‐TKI‐resistant lung adenocarcinoma. Interestingly, we found for the first time that YAP regulates p62 transcription through ERK, and YAP inhibition can suppress the expression of oncogenic p62. We also confirmed that the expressions of p62 and YAP have a positive correlation in EGFR‐mutant lung adenocarcinoma patients. To block cell survival via perturbing YAP‐p62 axis, we treated EGFR‐TKI‐resistant lung cancer cells with YAP inhibitor verteporfin. Remarkably, verteporfin effectively caused the death of EGFR‐TKI‐resistant lung cancer cells by decreasing the expressions of p62 with oncogenic function, YAP, and its target PD‐L1. So, the cumulative effect of oncogenic p62 should be considered when using autophagy inhibitors, especially drugs that act at the last stage of autophagy such as chloroquine and bafilomycin A1. Conclusion Finally, we suggest that targeting YAP‐p62 signaling axis can be useful to suppress the EGFR‐TKI‐resistant lung cancer. Therefore, drug repurposing of verteporfin for lung cancer treatment may be valuable to consider because it can inhibit critical targets: p62, YAP, and PD‐L1 at the same time.
Primary malignant melanoma (MM) accounts for 1% of all cancers, and only 3% to 7% of these tumors occur in the female genital tract. Data are limited with respect to the basis for treatment recommendations because of the rarity of MM. The overall prognosis of melanomas of the female genital tract is very poor. Two cases of MM of the female genital tract are presented. The first case is of a 70-year-old female patient who complained of left thigh pain and underwent magnetic resonance imaging that showed cervical cancer with involvement of the vagina, bladder, and parametrium, in addition to multiple bony metastases of the proximal femur, acetabulum, and both iliac bones. The second case is of a 35-year-old female patient who suffered from vaginal bleeding for 5 months, and she was diagnosed as having primary vaginal melanoma. The patient underwent radical surgery and two additional surgeries because of recurrence of cancer in both inguinal areas. After surgery, the patient received adjuvant immunotherapy, radiation therapy, and chemotherapy. In both the aforementioned cases, the pathologic diagnosis was made after immunohistochemical analysis, i.e., the tumor cells were stained with HMB-45 and S100, and were found to be positive for both immunostains.
This study evaluates the effectiveness and safety of moxibustion for benign prostatic hyperplasia (BPH). Methods: Using the keywords "benign prostatic hyperplasia", "benign prostatic hypertrophy", "benign prostatic enlargement", "prostatic hyperplasia", and "moxibustion", we searched papers in numerous databases, including
Background: Benign prostatic enlargement (BPE) causes discomfort in daily life, including lower urinary tract symptoms (LUTSs) caused by the enlarged prostate, and requires long-term management as a chronic, irreversible disease. To improve LUTS, certain complementary therapies have been used with or without doctors’ directions. Conventional treatments and complementary therapies tend to be combined unsystematically, depending on patient preference; thus, research for safe and efficient combination therapy is warranted. Methods: Twenty-nine participants were randomly assigned to an integrative group (IG, n = 15) or a conventional group (CG, n = 14). The IG received moxibustion (twice weekly for 4 weeks, at the acupuncture points SP6, LR3, and CV4) and conventional medication for 4 weeks, followed by conventional medication alone for 8 weeks. The CG received conventional medication alone for 12 weeks. The outcome measures were International Prostate Symptom Score (IPSS), patient's global impression of changes (PGIC), maximum urinary flow rate (Q max), postvoid residual urine volume (PVR), and frequency-volume chart. Results: Total IPSS (IG, −2.4 ± 4.2; CG, 0.9 ± 4.0; P = .039), PGIC-A (IG, 3.5 ± 1.0; CG, 2.2 ± 1.0; P = .001), and PGIC-B (IG, 3.5 ± 0.1; CG, 4.7 ± 0.6; P = .004) were significantly improved in the IG compared with the CG, 4 weeks after baseline. Among the IPSS items, incomplete emptying (IG, −0.6 ± 0.7; CG, 0.4 ± 1.2; P = .019), straining (IG, −0.6 ± 0.8; CG, 0.2 ± 1.2; P = .046), and nocturia (IG, −0.8 ± 1.4; CG, 0.1 ± 1.0; P = .045) showed significant differences. The Q max and PVR volume did not differ significantly at 12 weeks after the baseline. Conclusion: Moxibustion can be considered an adjunct therapy to improve LUTS in BPE patients. A full-sized randomized controlled trial would be feasible with comparator modifications and an extended study period. The study design should include a placebo group and narrow the eligibility to subjects who do not respond well to conventional treatments.
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