Surufatinib combined camrelizumab as a valuable third-line rescue therapy for a patient with extensive-stage for small-cell lung cancer: a case report and literature review.

Lung cancer is one of the most common malignant tumors with the highest incidence. Gene mutations are rare in small-cell lung carcinoma (SCLC), resulting in targeted therapy being only a third-line recommendation. Surufatinib (Sulanda) is an oral angio-immune kinase inhibitor used to treat solid tumors. We report a case of SCLC treated with surufatinib combined with camrelizumab, with good therapeutic results in our department. The patient experienced over 18 months of progression-free survival and over 28 months of overall survival. This suggests that surufatinib combined with camrelizumab is an effective third-line treatment for SCLC patients. However, the response rate to surufatinib treatment in all patients with SCLC remains unknown and needs to be determined in a large population.

Pathologic collision of urinary bladder urothelial carcinoma with small cell carcinoma: a case report.

BACKGROUND: Urothelial carcinoma is a major subtype of bladder cancer and small cell carcinoma (SCC) is a rare type of cancer in clinical practice. Pathologic collision of urinary bladder urothelial carcinoma with SCC is not common in clinical settings. CASE PRESENTATION: Here, we report a patient with high-grade papillary carcinoma which changed to collision tumor with SCC. The patient underwent radical cystectomy; however, neck and mediastinum lymph nodes metastases were detected 11 months after the operation. The lymph nodes were diagnosed pathologically as SCC. Chemoradiotherapy was subsequently prescribed. Unfortunately, this patient died of COVID-19 in early 2023. DISCUSSION: We hypothesized the mechanism underlying this pathological transformation. For patients with urothelial bladder cancer, pathological analysis should be conducted to allow standardized and persistent treatment. Moreover, drugs should be selected depending on the type of pathology, especially for patients who develop relapse, since collision tumor or other pathological tumors may be present. CONCLUSIONS: We recommend that radical cystectomy be performed early enough for patients with non-muscle invasive bladder cancer, who are at a high risk of tumor recurrence. However, this conclusion needs to be validated in a larger number of patients.

Radiation prevents tumor progression by inhibiting the miR­93­5p/EphA4/NF­κB pathway in triple­negative breast cancer.

Breast cancer (BC) is the most common type of cancer in women. Triple­negative BC (TNBC) constitutes 10­15% of all BC cases and is associated with a poor prognosis. It has previously been reported that microRNA (miR)­93­5p is dysregulated in plasma exosomes from patients with BC and that miR­93­5p improves radiosensitivity in BC cells. The present study identified EphA4 as a potential target gene of miR­93­5p and investigated the pathway related to miR­93­5p in TNBC. Cell transfection and nude mouse experiments were performed to verify the role of the miR­93­5p/EphA4/NF­κB pathway. Moreover, miR­93­5p, EphA4 and NF­κB were detected in clinical patients. The results revealed that EphA4 and NF­κB were downregulated in the miR­93­5p overexpression group. By contrast, EphA4 and NF­κB expression levels were not significantly altered in the miR­93­5p overexpression + radiation group compared with those in the radiation group. Furthermore, overexpression of miR­93­5p with concomitant radiation therapy significantly decreased the growth of TNBC tumors in vivo. In conclusion, the present study revealed that miR­93­5p targeted EphA4 in TNBC through the NF­κB pathway. However, radiation therapy prevented tumor progression by inhibiting the miR­93­5p/EphA4/NF­κB pathway. Therefore, it would be interesting to elucidate the role of miR­93­5p in clinical research.

Microarray data reveal potential genes that regulate triple-negative breast cancer.

OBJECTIVE: Triple-negative breast cancer (TNBC) is characterized by a lack of targeted therapies and poor patient prognosis, and its underlying pathological mechanisms remain unclear. This study aimed to identify potential key genes and related pathways that are required for TNBC development. METHODS: We screened the Gene Expression Omnibus database for transcriptome data and identified differently expressed genes in TNBC. Then, we performed Gene Ontology analysis to determine the genes and pathways involved in TNBC development. We correlated significantly expressed genes and miRNAs using miRDB, TargetScan, miRWalk, and DIANA, and then validated the expression of CDK1 and miR-143-3p in TNBC patients. RESULTS: Eighteen genes were significantly upregulated in TNBC patients, and these were found to be enriched in cell metabolic process, cell division, mitochondrion, and respiratory chain. MiR-143-3p was found to be an upstream regulator of CDK1. Validation experiments revealed that CDK1 was upregulated while miR-143-3p was downregulated in clinical TNBC specimens. CONCLUSIONS: Collectively, our results revealed 18 upregulated genes in TNBC. Notably, CDK1 and its related microRNA miR-143-3p could be potential therapeutic targets for TNBC.

A Case of Iodine 125 Seeds (I-125) Responding to Lung Squamous Cell Carcinoma.

Lung squamous cell cancer (SCC) and accounts for approximately 20%-30% of all lung cancers. Surgery, chemotherapy and radiotherapy are the main treatments for lung SCC patients. A case with lung SCC patient who was treated using iodine 125 seeds (I-125) because the location of the tumor was adjacent to the great vessels. I-125 is an ideal brachytherapy for lung SCC patients with large masses who lost the chance of operation. I-125 is an adjuvant therapy, combined with chemotherapy and molecular targeting therapy might serve to improve the prognosis of lung SCC patients.

The Treatment for a Patient with Cancer of Unknown Primary: A Case Report.

BACKGROUND: Cancer of unknown primary (CUP) is metastatic at diagnosis with an unknown primary site, indicating a high degree of malignancy with a poor prognosis. The development and application of targeted therapy and immunotherapy are current research hotspots, which provide additional treatment options for CUP. CASE PRESENTATION: A 36-year-old male presented with pain on the right hip in April 2018. After various examinations, he was diagnosed with CUP. This patient received chemotherapy, immunotherapy, and local radiotherapy in our department. However, the use of radiotherapy after immunotherapy resulted in severe pneumonia. CONCLUSION: Compared with traditional treatments, immunotherapy is an effective treatment with fewer side effects and better patient tolerance. However, treating physicians should be still pay special attention to the occurrence of side effects when radiotherapy is combined with immunotherapy.

Expression and Clinical Value of LncRNA GAPLINC in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The long noncoding RNA (lncRNA) GAPLINC, or gastric adenocarcinoma predictive long intergenic ncRNA, plays a carcinogenic role in a variety of different tumor types. There is limited information regarding the biological function of GAPLINC in the development of esophageal squamous cell carcinoma (ESCC). METHODS: Surgical tissue samples of 40 patients undergoing ESCC radical surgery were collected, including ESCC tissues and corresponding adjacent normal tissues. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of lncRNA GAPLINC in the human ESCC cell line (TE11). The function role of LncRNA GAPLINC was detected after specific siRNA interference and overexpression in the TE11 cell line. The effects of LncRNA GAPLINC on ESCC cell proliferation, migration and invasion abilities were investigated by flow cytometry, using the Cell Counting Kit-8 (CCK-8), and by Transwell migration assays, respectively. RESULTS: The expression of lncRNA GAPLINC in ESCC tissues was significantly higher than that in corresponding adjacent normal tissues (P<0.05) and correlated with the degree of tumor differentiation (P<0.05). Compared with human esophageal normal epithelial cell lines, the expression of LncRNA GAPLINC was significantly higher in the human ESCC cell line (P<0.05). CCK-8 assays showed that LncRNA GAPLINC overexpression increased the growth rate of cells (P<0.05). Transwell experiments showed that LncRNA GAPLINC overexpression increased the ability of cell migration and invasion compared to control cells (P<0.05). Annexin V assay revealed that LncRNA GAPLINC silencing increased early stage apoptosis (P<0. 05). CONCLUSION: Our results suggest that LncRNA GAPLINC may be used as a biomarker for the diagnosis and monitoring of ESCC, and may play an oncogenic role in ESCC.

Assessment of the value of adjuvant radiotherapy for treatment of gastric adenocarcinoma based on pattern of post-surgical progression.

PURPOSE: To assess the value of adjuvant radiotherapy for treatment of gastric adenocarcinoma and to investigate subgroups of patients suitable for adjuvant radiotherapy. METHODS AND MATERIALS: Data from 785 patients with gastric adenocarcinoma who had undergone D1/D2 radical resection and adjuvant chemotherapy were collected, the site of first progression was determined, and the relationship between the rate of local recurrence and clinicopathologic features was analyzed. RESULTS: By the end of the follow-up period, progression was observed in 405 patients. Local recurrence was observed as the first progression in 161 cases. The local recurrence rate was significantly lower than the non-local progression rate (20.5% vs 31.5%, p=0.007). Multivariate Cox regression analysis showed a significant relationship among degree of differentiation, T stage, N stage, and rate of local recurrence. CONCLUSIONS: Not all patients with gastric carcinoma required adjuvant radiotherapy. However, patients with poorly differentiated cancer cells, advanced T stage (T3/T4), and positive lymph nodes, which included patients in the T4N1-2M0 subgroup, were recommended for adjuvant radiotherapy.

Investigation of miR-93-5p and its effect on the radiosensitivity of breast cancer.

Accumulating evidence suggests that intrinsic resistance to radiotherapy reduces the survival of patients with cancer. The present study investigated whether miR-93-5p affects proliferation, migration, apoptosis, and radiosensitivity of breast cancer (BC) cells. MDA-MB-468, MCF-7, and MDA-MB-231 BC cells were incubated with hsa-miR-93-5p mimics, hsa-miR-93-5p inhibitor, and negative control RNA with or without exposure to ionizing radiation to determine cell proliferation, migration, and apoptosis using the Cell Counting Kit-8 assay, wound healing assay and apoptotic assay, respectively. Overexpression of miR-93-5p inhibited the migratory abilities (P = 0.001) and decreased the cell proliferation (P = 0.049) of MCF-7 cells. In MCF-7 cells, a significant increase in apoptosis was detected after treatment with miR-93-5p compared with the negative control (P = 0.001) and miR-93-5p inhibitor (P = 0.004). In MDA-MB-468 cells, the proportion of apoptotic cells increased following exposure to ionizing radiation (P = 0.001). The percentage of apoptotic MDA-MB-231 cells in the miR-93-5p group was significantly increase compared with that determined in the negative control (P = 0.044) and hsa-miR-93-5p inhibitor (P = 0.046) groups. In conclusion, our findings showed that miR-93-5p reduces BC cell proliferation and migratory capacity, and increases the ratio of apoptotic cells. Overexpression of miR-93-5p could increase radiosensitivity in BC cells by increasing apoptosis. This evidence provides new insight into the treatment of BC and identifies miR-93-5p as a potential therapeutic target.

Success of 125I-Seed Treatment in Vulvar Squamous-Cell Carcinoma with Aplastic Anemia: A Case Report.

Vulvar squamous-cell carcinoma (SCC) is a rare disease that occurs mainly in postmenopausal women. Chemo/radiotherapy with or without surgery is the most important modality for treatment of advanced vulvar cancer. A case of vulvar SCC with aplastic anemia was treated using 125I seeds in our department, because surgery and chemotherapy were not possible due to low platelets, leaving radiotherapy as the lone therapeutic option. 125I seeds present an alternative option for treatment of patients with vulvar SCC and local relapse with lymph-node metastasis following previous radiotherapy.

Immunotherapy Combined with Chemotherapy as a Promising Therapy for a EGFR Exon 19 Deletion with MET Amplification Patient with Non-Small-Cell Lung Cancer: A Case Report.

Advanced non-small-cell lung cancer (NSCLC) patients with EGFR exon 19 deletion often get benefits from the treatment of tyrosine kinase inhibitors (TKI). In the same way, the NSCLC patients with mesenchymal-to-epithelial transition (MET) amplification get benefits from crizotinib. The treatment becomes extremely difficult for the patients with both EGFR exon 19 deletion and MET amplification, after failure of first-line TKI. An advanced NSCLC patient with EGFR exon 19 deletion was treated with TKI. However, the disease recurred after four months. MET amplification was found after biopsy again. The patient was treated with the combination of crizotinib, while the disease recurred after eight months. The patient was treated by pembrolizumab and pemetrexed + carboplatin chemotherapy as salvage therapy. The therapeutic effect has been remarkable up to present. In conclusion, immunotherapy combined with chemotherapy could be a promising therapy for the NSCLC patients with both EGFR exon 19 deletion and MET amplification after the failure of first-line TKI treatment. Thus, further insights into the variant genes contribute to NSCLC treatment.

Case Report: Herceptin as a Potentially Valuable Adjuvant Therapy for a Patient With Human Epidermal Growth Factor Receptor 2-Positive Advanced Esophageal Squamous Cell Carcinoma.

Esophageal cancer is one of the most common cancers with a low overall 5-year relative survival rate of approximately 20%. Trastuzumab (Herceptin®) targets HER2 and is an effective therapeutic strategy in HER2-positive breast cancer. However, few reports have described targeted therapy for treating esophageal squamous cell carcinoma (ESCC). A patient with advanced ESCC who had received chemotherapy, radiotherapy, and had undergone a clinical study is described here. The tumor had not been controlled. Herceptin and chemotherapy were used as salvage therapy in this patient because of high HER2 expression. Good therapeutic results were observed in this patient. Therefore, Herceptin is a potential target therapy for patients with HER2-positive advanced ESCC. A study with a large population and a prospective random study are necessary to validate these results.

Author Correction: Different signatures of miR-16, miR-30b and miR-93 in exosomes from breast cancer and DCIS patients.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Downregulated lncRNA UCA1 acts as ceRNA to adsorb microRNA-498 to repress proliferation, invasion and epithelial mesenchymal transition of esophageal cancer cells by decreasing ZEB2 expression.

Objective: Esophageal cancer (EC) is one of the most general malignant tumors in humans. There were few studies researching the connections between lncRNA UCA1 and EC. This study is to research the effect of lncRNA UCA1 adsorbing microRNA-498 (miR-498) as a ceRNA to regulate ZEB2 expression on epithelial mesenchymal transition (EMT), invasion and migration of EC cells. Methods: UCA1, miR-498 and ZEB2 expression in EC tissues and cells was detected by RT-qPCR or western blot analysis. EC cells were transfected with siRNA-UCA1, miR-498 mimics or their controls to determine cell colony, proliferation, cycle distribution, apoptosis, migration and invasion by colony formation assay, CCK-8 assay, flow cytometry, and Transwell assay, respectively. The protein expression of PCNA, c-Myc, E-cadherin, N-cadherin, MMP-2 and MMP-9 was detected by Western blot analysis. The growth rate and weight of transplanted tumor in nude mice were observed. Results: There were overly expressed UCA1 and ZEB2 and lowly expressed miR-498 in EC tissues and cells. LncRNA UCA1 acted as ceRNA to inhibit miR-498 expression and thereby increasing ZEB2 expression. With down-regulated UCA1 and up-regulated miR-498, ZEB2 expression, cell proliferation, colony formation, invasion, migration ability, EMT, tumor growth rate and weight in nude mice were apparently reduced. Conclusion: This study demonstrates that inhibited UCA1 up-regulated miR-498 and down-regulated ZEB2, thereby repressing proliferation activity, invasion, migration, and EMT of EC cells.

Exosomal microRNAs as tumor markers in epithelial ovarian cancer.

Specific microRNAs (miRNAs) are packaged in exosomes that regulate processes in tumor development and progression. The current study focuses on the influence of exosomal miRNAs in the pathogenesis of epithelial ovarian cancer (EOC). MiRNA profiles were determined in exosomes from plasma of 106 EOC patients, eight ovarian cystadenoma patients, and 29 healthy women by TaqMan real-time PCR-based miRNA array cards containing 48 different miRNAs. In cell culture experiments, the impact of miR-200b and miR-320 was determined on proliferation and apoptosis of ovarian cancer cell lines. We report that miR-21 (P = 0.0001), miR-100 (P = 0.034), miR-200b (P = 0.008), and miR-320 (P = 0.034) are significantly enriched, whereas miR-16 (P = 0.009), miR-93 (P = 0.014), miR-126 (P = 0.012), and miR-223 (P = 0.029) are underrepresented in exosomes from plasma of EOC patients as compared to those of healthy women. The levels of exosomal miR-23a (P = 0.009, 0.008) and miR-92a (P = 009, 0.034) were lower in ovarian cystadenoma patients than in EOC patients and healthy women, respectively. The exosomal levels of miR-200b correlated with the tumor marker CA125 (P = 0.002) and patient overall survival (P = 0.019). MiR-200b influenced cell proliferation (P = 0.0001) and apoptosis (P < 0.008). Our findings reveal specific exosomal miRNA patterns in EOC and ovarian cystadenoma patients, which are indicative of a role of these miRNAs in the pathogenesis of EOC.

Different signatures of miR-16, miR-30b and miR-93 in exosomes from breast cancer and DCIS patients.

Loading of microRNAs (miRNAs) into exosomes that are involved in cellular communication is a selective process. The current study investigates whether the enrichment of miRNAs in exosomes reflects the pathogenesis of breast cancer (BC) and ductal carcinoma in situ (DCIS). The levels of miRNAs were quantified in exosomes from plasma of 32 BC patients, 8 DCIS patients and 8 healthy women by TaqMan real-time PCR-based miRNA array cards containing 47 different miRNAs. Then, exosomal miR-16, miR-30b and miR-93 that displayed deregulation in the arrays were selected and analyzed in 111 BC patients, 42 DCIS patients and 39 healthy women by TaqMan real-time PCR. Identification of exosomes was performed by Western blot. The levels of exosomal miR-16 were higher in plasma of BC (p = 0.034) and DCIS (p = 0.047) patients than healthy women, and were associated with estrogen (p = 0.004) and progesterone (p = 0.008) receptor status. Particularly, in estrogen-positive patients miR-16 was significantly enriched in exosomes (p = 0.0001). Lower levels of exosomal miR-30b were associated with recurrence (p = 0.034). Exosomal miR-93 was upregulated in DCIS patients (p = 0.001). Our findings suggest that different signatures of miR-16, miR-30b and miR-93 in exosomes from BC and DCIS patients are associated with a particular biology of breast tumors.