CN-121971622-A - BLVRB application in treating gallbladder cancer

CN121971622ACN 121971622 ACN121971622 ACN 121971622ACN-121971622-A

Abstract

The disclosure belongs to the technical field of biological medicine, and particularly relates to an application of BLVRB in treating gallbladder cancer. The present disclosure provides an early diagnostic protein marker for gallbladder cancer with high specificity and sensitivity. The mechanism of BLVRB and tumor proliferation progress is studied for the first time in human gallbladder cancer, and the method has potential value as a treatment target. The present disclosure for the first time found that BLVRB regulates downstream genes by nuclear translocation, acting as transcription factors, rather than relying on their known metabolic enzyme functions. The disclosure also provides a medicine for treating cholecystocarcinoma, a kit and application thereof. The method can fill the gap that the protein marker with high diagnosis efficiency does not exist at present in the cholecystokinis, and has great clinical significance.

Inventors

GAO ZHIHUI
LI NA
XIAO JIE
SHEN SHENG
NI XIAOJIAN
LIU HOUBAO

Assignees

复旦大学附属中山医院

Dates

Publication Date: 20260505
Application Date: 20260212

Claims (10)

1. Use of BLVRB in the treatment of gallbladder cancer, said use comprising at least one of: (1) Use in the preparation of a product for inhibiting proliferation and/or clonogenic activity of gallbladder cancer cells; (2) Use in the manufacture of a product for inhibiting proliferation of gallbladder cancer cells by inhibiting the pentose phosphate pathway; (3) Use in the manufacture of a product for inhibiting the progression of gallbladder cancer by increasing antioxidant capacity; (4) Use in the manufacture of a product for inhibiting the progression of gallbladder cancer by modulating a downstream gene by BLVRB nuclear translocation; (5) Use in the manufacture of a product for early screening and/or diagnostic assessment of gallbladder cancer; (6) Use as a biomarker for early screening and/or diagnostic assessment of gallbladder cancer; (7) The application of the kit serving as a target for treating early stage cholecyst cancer.
2. The use according to claim 1, wherein BLVRB participates in the pathological process of gall bladder cancer by a plurality of functional mechanisms, and wherein the BLVRB functions as at least one of the following: (1) Said BLVRB inhibits the proliferation and/or clonogenic activity of gallbladder cancer cells; (2) The BLVRB has the advantages that the expression of BLVRB is down-regulated to inhibit the antioxidation capability, so that the proliferation and tumor growth of gallbladder cancer cells in vitro and in vivo are promoted; (3) The down regulation of BLVRB expression enhances the activity of pentose phosphate pathway, and further increases the proliferation capacity of gallbladder cancer cells through pentose phosphate pathway; (4) Said BLVRB affects the pentose phosphate pathway by a non-bilirubin metabolic regulation mechanism; (5) The down-regulation of BLVRB reduces the transcriptional co-inhibition of G6PDH, thereby increasing the transcriptional level of pentose phosphate pathway related metabolic enzymes and promoting the proliferation of gallbladder cancer cells; (6) The BLVRB controls downstream genes by nuclear translocation into the nucleus to inhibit gallbladder cancer progression.
3. The use of claim 1, wherein the product comprises one or more of a drug, a reagent, a kit, a chip, a test strip, a membrane strip, a detection platform.
4. The use according to claim 1, wherein the test sample for which the product is directed is a tissue sample of a subject, a body fluid sample including serum, circulating tumor cells, bile or blood-derived outer vesicles.
5. A medicament for treating gallbladder cancer, wherein the medicament increases BLVRB expression levels in a patient, and further wherein the medicament comprises at least one of: (1) BLVRB lentivirus or adenovirus over-expression strain; (2) Inducing BLVRB endogenous up-regulated small molecular substances, and further, at least one of decitabine, RG108, vorinostat and trichostatin A; (3) An agonist that upregulates BLVRB transcription or apparent levels, further, the agonist is selected from at least one of CDDO-Me, TNF- α.
6. The medicament according to claim 5, further comprising a pharmaceutically acceptable carrier or adjuvant, further wherein the medicament is used alone or in combination with other medicaments.
7. A kit for early screening and/or diagnostic evaluation of gallbladder cancer, which is characterized in that the kit at least comprises a reagent for detecting BLVRB expression quantity.
8. The kit of claim 7, further comprising one or more of a positive reference, a negative reference, a buffer, an enzyme, and a detectable label.
9. The application of the reagent for detecting BLVRB expression quantity in preparing the early stage screening and/or diagnosis and evaluation kit for cholecyst cancer.
10. A system for early screening and/or diagnostic assessment of gallbladder cancer, comprising a sample collection device, a separation device, a sample detection device, and a diagnostic device, wherein: The sample collection device is configured to collect a detection sample of a subject, the separation device is configured to separate a device containing BLVRB to-be-detected objects from the detection sample, the sample detection device comprises a device capable of detecting BLVRB expression levels in the to-be-detected objects, the diagnosis device comprises a memory and a processor, the memory stores a computer program, and the processor is configured to execute the computer program stored in the memory so as to judge whether the subject contains gallbladder cancer according to detection values of BLVRB expression levels in the detection sample of the subject.

Description

BLVRB application in treating gallbladder cancer Technical Field The disclosure belongs to the technical field of biological medicine, and particularly relates to an application of BLVRB in treating gallbladder cancer. Background The gall bladder cancer has a low proportion of less than 1% in all malignant tumors of the whole body, belongs to clinical rare cancers, is a fifth common digestive tract tumor in the global scope, has a global annual incidence rate of 1-2/10 ten thousand, is a common biliary tract system tumor, has a proportion of 80-95% of the malignant tumors of the whole biliary tract system, and has extremely high malignancy. Late diagnosis and poor prognosis are major problems in diagnosis and treatment of gallbladder cancer, and survival rate of 5 years has not been satisfactorily improved in recent years. Radical cholecystectomy is one of the most effective treatments at present, achieving R0 excision with a long survival time, but most patients already have middle and late stages in diagnosis, losing the opportunity for radical surgical treatment. How to diagnose the precancerous lesions of the gallbladder and the gallbladder cancer in advance is a great challenge for improving the survival rate of patients with the gallbladder cancer. Therefore, the high-efficiency biomarker which is helpful for early diagnosis of the precancerous lesions of the gallbladder and the gallbladder cancer is found, and the method has important significance for early diagnosis, early surgical intervention and early treatment of patients with the gallbladder cancer in clinical work. In addition to this, tumor biological properties and stage are also important predictors affecting patient survival. The biological behaviour of tumors is one of the key directions for studying gallbladder cancer, approximately 95% of which originate in epithelial cells, adenocarcinomas are the major histological type, and pathogenesis generally follows the order dysplasia-adenoma-carcinoma. The size of gallbladder polypoid lesions is a point of particular clinical concern, suggesting excision of gallbladder polyps greater than 1cm for prevention of gallbladder cancer. Although there is controversy over the threshold criteria for resecting gallbladder polypoid lesions, the non-contending fact is that gallbladder polyps less than 1cm in diameter after surgery rarely turn out to be a tumor, in contrast to the significantly increased probability that polyp pathologies greater than 1cm turn out to be malignant. Thus, abnormal proliferation may be one of the important biological behavioral changes in early stages of cholecystokinis. At present, research on proliferation in gall bladder tumors is mainly focused on the tumor development period, and researches on abnormal proliferation is started in early stage of tumorigenesis, and then nutrition requirements such as glucose and the like are increased and cytoprotection mechanisms after excessive proliferation are freshly reported. Therefore, the development of the early diagnosis protein marker for the cholecystokinis with high specificity and sensitivity has important clinical significance. Disclosure of Invention The purpose of the disclosure is to research the proliferation, progress, prediction and treatment value of BLVRB in gall bladder cancer, and provide the application value of BLVRB in gall bladder cancer diagnosis and treatment. Meanwhile, the action mechanism of BLVRB for promoting proliferation in cholecystokinin cancer through pentose phosphate pathway has not been reported yet. The aim of the disclosure is achieved by the following technical scheme: In a first aspect of the present disclosure, the present disclosure provides a use of BLVRB in the treatment of gallbladder cancer, the use comprising at least one of: (1) Use in the preparation of a product for inhibiting proliferation and/or clonogenic activity of gallbladder cancer cells; (2) Use in the manufacture of a product for inhibiting proliferation of gallbladder cancer cells by inhibiting the pentose phosphate pathway; (3) Use in the manufacture of a product for inhibiting the progression of gallbladder cancer by increasing antioxidant capacity; (4) Use in the manufacture of a product for inhibiting the progression of gallbladder cancer by modulating a downstream gene by BLVRB nuclear translocation; (5) Use in the manufacture of a product for early screening and/or diagnostic assessment of gallbladder cancer; (6) Use as a biomarker for early screening and/or diagnostic assessment of gallbladder cancer; (7) The application of the kit serving as a target for treating early stage cholecyst cancer. In some embodiments of the disclosure, the BLVRB participates in the pathological process of gall bladder cancer through a plurality of functional mechanisms, and the function of the BLVRB is at least one of the following: (1) Said BLVRB inhibits the proliferation and/or clonogenic activity of gallbladder cancer cells; (2) The