Case report: Pilomatrix carcinoma with PDL1 expression and CDKN2A aberrant.

Case report: A 55-year-old male patient developed a mass in the left inguinal area with left lower limb swelling and first visited a local hospital 3 months earlier because of unrelieved pain. An MRI scan suggested left suprapubic branch and left acetabular bone destruction, abnormal soft tissue signals within the iliopsoas muscle of the anterior edge of the left iliac bone, and enlarged lymph nodes in the left iliac fossa and left inguinal region. The patient subsequently underwent left pelvic lesion open biopsy and inguinal lymph node resection biopsy. According to pathological reports, the left inguinal mass was considered to be a malignant tumor of cutaneous accessory origin (pilomatrix carcinoma) with extensive vitreous changes. The suprapupubis branch mass was considered to be a bone metastatic pilomatrix carcinoma. Immunohistochemistry (IHC) revealed a PDL1 combined positive score (CPS) of 8. DNA next-generation sequencing (NGS) showed CDKN2A L65Rfs*53 mutation. The patient received three cycles of gemcitabine and nedaplatin. However, the lesion progressed. Conclusion: Chemotherapy is not effective for treating pilomatrix carcinoma. PDL1 antibodies and CDK4/6 inhibitors might be treatment options for pilomatrix carcinoma.

A Non-G-Quadruplex DNA Aptamer Targeting NCL for Diagnosis and Therapy in Bladder Cancer.

Bladder cancer (BC) is a highly aggressive malignant tumor affecting the urinary system, characterized by metastasis and a poor prognosis that often leads to limited therapeutic success. This study aims to develop a novel DNA aptamer for the diagnosis and treatment of BC using a tissue-based systematic evolution of ligands by an exponential enrichment (SELEX) process. By using SELEX, this work successfully generates a new aptamer named TB-5, which demonstrates a remarkable and specific affinity for nucleolin (NCL) in BC tissues and displays marked biocompatibility both in vitro and in vivo. Additionally, this work shows that NCL is a reliable tissue-specific biomarker in BC. Moreover, according to circular dichroism spectroscopy, TB-5 forms a non-G-quadruplex structure, distinguishing it from the current NCL-targeting aptamer AS1411, and exhibits a distinct binding region on NCL compared to AS1411. Notably, this study further reveals that TB-5 activates NCL function by promoting autophagy and suppressing the migration and invasion of BC cells, which occurs by disrupting mRNA transcription processes. These findings highlight the critical role of NCL in the pathological examination of BC and warrant more comprehensive investigations on anti-NCL aptamers in BC imaging and treatment.

Targeting tumor endothelial cells with methyltransferase inhibitors: Mechanisms of action and the potential of combination therapy.

Tumor endothelial cells (TECs) reside in the inner lining of blood vessels and represent a promising target for targeted cancer therapy. DNA methylation is a chemical process that involves the transfer of a methyl group to a specific base in the DNA strand, catalyzed by a DNA methyltransferase (DNMT). DNMT inhibitors (DNMTis) can inhibit the activity of DNMTs, thereby preventing the transfer of methyl groups from s-adenosyl methionine (SAM) to cytosine. Currently, the most viable therapy for TECs is the development of DNMTis to release cancer suppressor genes from their repressed state. In this review, we first outline the characteristics of TECs and describe the development of tumor blood vessels and TECs. Abnormal DNA methylation is closely linked to tumor initiation, progression, and cell carcinogenesis, as evidenced by numerous studies. Therefore, we summarize the role of DNA methylation and DNA methyltransferase and the therapeutic potential of four types of DNMTi in targeting TECs. Finally, we discuss the accomplishments, challenges, and opportunities associated with combination therapy with DNMTis for TECs.

Neoadjuvant immunotherapy, chemotherapy, and combination therapy in muscle-invasive bladder cancer: A multi-center real-world retrospective study.

To parallelly compare the efficacy of neoadjuvant immunotherapy (tislelizumab), neoadjuvant chemotherapy (gemcitabine and cisplatin), and neoadjuvant combination therapy (tislelizumab + GC) in patients with muscle-invasive bladder cancer (MIBC) and explore the efficacy predictors, we perform a multi-center, real-world cohort study that enrolls 253 patients treated with neoadjuvant treatments (combination therapy: 98, chemotherapy: 107, and immunotherapy: 48) from 15 tertiary hospitals. We demonstrate that neoadjuvant combination therapy achieves the highest complete response rate and pathological downstaging rate compared with neoadjuvant immunotherapy or chemotherapy. We develop and validate an efficacy prediction model consisting of pretreatment clinical characteristics, which can pinpoint candidates to receive neoadjuvant combination therapy. We also preliminarily reveal that patients who achieve pathological complete response after neoadjuvant treatments plus maximal transurethral resection of the bladder tumor may be safe to receive bladder preservation therapy. Overall, this study highlights the benefit of neoadjuvant combination therapy based on tislelizumab for MIBC.

Clinical Effect of Retroperitoneal Laparoscopic Radical Nephrectomy on Renal Cell Carcinoma, the Influence of Renal Function, and the Influencing Factors of Recurrence.

Renal cell carcinoma is abbreviated as renal carcinoma, and its clinical symptoms are basically hematuria, lumbago, and abdomen bump. As people's lifestyles change, the incidence of renal carcinoma continues to rise due to factors such as smoking and obesity. At present, surgical treatment is mostly used in clinical practice. Traditional open radical nephrectomy (ORN) is one of the main methods for clinical treatment of renal carcinoma. However, due to its large wound and large amount of intraoperative blood loss, the renal function of patients after surgery is poor, which is not conducive to the postoperative recovery of patients. Retroperitoneal laparoscopic radical nephrectomy (RLRN) has been widely used in the surgical treatment of renal cancer due to its advantages of small wound, less bleeding, and rapid recovery. The purpose of this study was to investigate the efficacy of RLRN in the treatment of renal cancer patients and its effect on renal function and to analyze the related factors affecting postoperative recurrence of patients. We adopt ORN and RLRN, two kinds of treatment, in patients with renal cancer surgery way, contrast analysis of the two groups of operation time, intraoperative blood loss, postoperative intestinal function recovery time, drainage tube indwelling time, length of hospital stay, and other clinical indicators and renal function indexes and use the single factor analysis and multifactor analysis, the relevant factors that affect kidney cancer patients with postoperative recurrence. The results showed that, compared with ORN treatment, RLRN treatment of renal cancer patients has a short operation time, less trauma, quick recovery after surgery, and fewer complications and can effectively alleviate the renal function injury and the body's inflammatory response, which is worthy of promotion. Postoperative recurrence was related to age, tumor diameter, TNM stage, surgical method, and postoperative immunotherapy.

SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer.

BACKGROUND: Almost all metastatic hormone-sensitive prostate cancers (mHSPC) will develop into metastatic castration-resistant prostate cancer (mCRPC) after androgen deprivation therapy (ADT). The expression level of squalene monooxygenase (SQLE) is increased in CRPC cells and regulates cholesterol metabolism. This study verified the biological function and mechanisms of SQLE in CRPC. METHODS: The expression of SQLE in human prostate cancer cells was overexpressed or silenced and its efficacy on cell survival was determined by the MTS test. Energy metabolism phenotype test was evaluated by XF real-time ATP rate assay, XF cell mitochondrial stress test, XF glycolysis stress test and XF mito fuel flex test. Cell migration and invasion were evaluated by colony formation assays and transwell assays; the expression of mRNA and protein was assessed by RT-qPCR and Western blot, respectively. Moreover, BALB/c nude mice model was performed to evaluate the lymph node metastasis. RESULTS: In our study, we found that the expression level of SQLE was significantly increased in bicalutamide-resistant-C4-2B cells compared to LNCaP cells. SQLE knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and reduced lymph node metastasis by inhibiting fatty acid oxidation in mitochondria. We also found that terbinafine, the specific inhibitor of SQLE, can enhance the sensitivity of prostate cancer cells to bicalutamide. CONCLUSION: Our study revealed that SQLE is involved in the progression of castration resistance in CRPC through mediating metabolic reprogramming, presenting SQLE as a new target for the treatment of mCRPC.

Chemo-drug Controlled-release Strategies of Nanocarrier in the Development of Cancer Therapeutics.

Nanoparticles are widely used in cancer therapy because of their nanoscale, high surface ratio, multifunctionality and so on. With specific construction of nanoparticles, by choosing magnetic nanomaterials or citric acid-coated nanoparticle, scientists can kill tumor cells effectively and accurately, importantly reducing the side effects of conventional chemotherapy. Scientists not only have designed nanoparticles loaded with therapeutic drugs, but also those equipped with targeted molecules. These works have made nanoparticles multifunctional nanocarriers. As multifunctional nanocarriers, nanoparticles play an important role of drug delivery and normally, enabling drug delivery to tumor tissues is a difficult task. During the period of internal circulation, it is hard to maintain the stability of the nanocarriers not attached to normal cells or serum. With the application of stimulus-responsive nanomaterials, scientists have developed many nanocarriers with controllable drug release. These controllable drug delivery systems can quickly respond to microenvironmental changes (PH, enzyme, etc.) or external stimuli (photo, heat, magnetic or electric fields). Thus, to overcome the side effects of controllable drug delivery systems in vivo, in this article, we summarize the various kinds of stimulus-responsive nanocarriers for cancer therapy and discuss the possibilities and challenges in future application.

Three-Dimensional Physical Model-Assisted Planning and Navigation for Laparoscopic Partial Nephrectomy in Patients with Endophytic Renal Tumors.

Resection of completely endophytic renal tumors is a huge challenge for surgeons due to a lack of definite visual clues, especially in the laparoscopic approach. Three-dimensional (3D) kidney models, which can illustrate the clear relationship between renal masses and surrounding health tissues, were considered as reliable tools for understanding renal tumor characteristics in previous studies. We hypothesized that 3D kidney models can be used not only for planning but also for navigating laparoscopic partial nephrectomy (LPN) in patients with completely endophytic renal tumors. In this study, we successfully constructed five cases of 3D kidney models for assisted planning and navigation for LPN in endophytic renal tumors. The renal masses and surrounding normal parenchyma of the patient-specific 3D models were dyed by different colorants for clear illustration. All patients experienced acceptable perioperative outcomes, and no patient suffered serious relative complications. The 3D kidney models were considered as a reliable tool based on clinical outcome and postoperative questionnaire results. This study is the first report of 3D kidney models for patients with completely endophytic tumors. 3D kidney models can aid surgeons in understanding the characteristics of renal tumors and potentially support assisted planning and performance of LPN in endophytic tumor cases.

Renal metastasis from cervical carcinoma presenting as a renal cyst: A case report.

In the present study, the case of a 51-year-old female with a metastatic tumor in the left kidney originating from cervical carcinoma, is reported. The patient had undergone chemoradiotherapy for stage IIB squamous-cell carcinoma of the uterine cervix 3 years earlier. Computed tomography (CT) identified low-density left renal nodules, which were diagnosed post-operatively as renal cysts during the follow-up conducted 2 years later. The next year, the patient was admitted to the Hunan Provincial Tumor Hospital (The Affiliated Tumor Hospital of Xiangya Medical College, Central South University, Changsha, Hunan, China) with a fever of unknown origin, left-sided flank pain and hematuria. CT examination detected irregular low-density nodules in the left kidney and heterogeneous enhancement on enhanced CT. Subsequently, the patient was subjected to a nephrectomy. Post-surgical analysis of subsequent biopsies indicated kidney tumor metastasis originating from cervical carcinoma. Renal metastases are rare in patients with cervical carcinoma. The present study reported a case of renal metastasis originating from cervical carcinoma and also reviewed previous case reports on patients presenting with this unusual type of cancer.

[Roles of adenosine and cytokines in the prostate tissue of rats with acute bacterial prostatitis].

OBJECTIVE: To investigate the possible roles of adenosine and the cytokines TNF-alpha and IL-10 in the pathogenesis of acute bacterial prostatitis (ABP) in rats. METHODS: Forty-eight male Wistar rats were randomly divided into groups A (ABP), B (ABP + theophylline intervention), C (sham) and D (blank control). ABP models were established by injecting Escherichia coli 0157 into the prostate, and those in group B were treated by intraperitoneal injection of theophylline immediately after modeling. At 4 and 14 days, the prostate tissues of the rats were collected for detection of the expressions of TNF-alpha and IL-10 by immunohistochemistry and the concentration of adenosine by high-performance liquid chromatography. RESULTS: At 4 and 14 days, the concentrations of adenosine were significantly higher in group A ([48.38 +/- 17.27] and [26.54 +/- 11.22] microg/g) than in C ([0.45 +/- 0.25] and [0.46 +/- 0.29] microg/g) and D ([0.41 +/- 0.23] and [0.43 +/- 0.27] microg/g) (P < 0.05), and so were the expressions of TNF-alpha in A (0.23 +/- 0.08 and 0.21 +/- 0.03) than in C (0.07 +/- 0.03 and 0.07 +/- 0.01) and D (0.07 +/- 0.06 and 0.07 +/- 0.06) (P < 0.05), and those of IL-10 in A (0.13 +/- 0.03 and 0.25 +/- 0.01) than in C (0.07 +/- 0.03 and 0.07 +/- 0.03) and D (0.07 +/- 0.01 and 0.07 +/- 0.02) (P < 0.05). Compared with group A, the rats in group B showed significant increases at 4 and 14 days in the severity of inflammation, concentration of adenosine ([86.64 +/- 32.87] and [51.17 +/- 22.96] microg/g, P < 0.05) and expression of TNF-alpha (0.37 +/- 0.08 and 0.32 +/- 0.06, P < 0.05), but exhibited no remarkable difference in the expression of IL-10 (0.12 +/- 0.06 and 0.15 +/- 0.06, P > 0.05). CONCLUSION: Adenosine may affect the progression of inflammation by regulating the expressions of the cytokines TNF-alpha and IL-10 in ABP rats through the adenosine receptor signaling pathway.

[Clinical features of acute urine retention in patients with benign prostate hyperplasia].

OBJECTIVE: To explore the clinical features of acute urine retention (AUR) ocurring in patients with benign prostate hyperplasia (BPH). METHODS: Clinical data from 548 patients diagnosed with BPH were retrospectively studied, and the clinical parameters of these patients with or without AUR were analyzed by statistical methods. RESULTS: Development of AUR was found in 164 patients (29.9%). Patients' age, IPSS, maximum flow rate (Q(max)), residual urine volume, prostate volume, transition zone volume, prostate-specific antigen (PSA) density, total PSA (tPSA) and free PSA (fPSA) including the ratio of free to total PSA(f/tPSA) were significantly different in the 2 groups (P<0.05), while there were no significant differences in the disease duration and transition zone index between the 2 groups (P>0.05). Multivariate logistic regression analysis showed that IPSS score, residual urine volume, tPSA, and Q(max) were risk factors for predicting the development of AUR. CONCLUSION: BPH patient's age, IPSS, Q(max), residual urine volume, prostate volume, transition zone volume, tPSA and fPSA, and PSA density all influence the occurrence of AUR, in which symptom severity, residual urine volume, total PSA and Q(max) are the principal risk factors for prognosing AUR.

[Causes, location and management of BPH surgery-related urethral stricture].

OBJECTIVE: To analyze the possible causes of BPH surgery-related urethral stricture and summarize the experience in its clinical management. METHODS: The clinical data of 37 cases of BPH surgery-related urethral stricture were analyzed retrospectively. The patients averaged 68.5 years in age, of whom 12 had the history of open surgery, and 25 transurethral surgery. Anterior urethral stricture was found in 6 cases, and posterior urethra in stricture 31. Thirty-five cases were treated by holmium laser urethrotomy (HLU) or a combination of HLU with transurethral resection of the scar in the stenotic segment, and the results were evaluated based on the maximum flow rate (Qmax). RESULTS: Two cases of full penile urethral stricture were treated by urinary diversion, and all the rest by urethral stricture surgery. Catheters were indwelt in 4 cases of urethral stenosis for 5-7 days post-operatively, and smooth urination was achieved after their removal, with a Qmax of > 15 ml/s. Another 31 cases of membranous urethral stricture received catheter indwelling of 2 -4 weeks and were followed up for 1 - 21 (mean 11. 5) months, of whom 23 experienced satisfactory voiding, with an average Qmax of 14.3 ml/s, and the other 8 poor voiding, with a Qmax of < 8 ml/s. CONCLUSION: HLU or a combination of HLU with transurethral resection of the scar in the stenotic segment is an effective method for the treatment of BPH surgery-related urethral stricture. And conscientiously performed BPH surgery can reduce the incidence of urethral stricture.