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PubMed2024

SPOP expression is associated with tumor-infiltrating lymphocytes in pancreatic cancer.

BACKGROUND: Speckle Type POZ Protein (SPOP), despite its tumor type-dependent role in tumorigenesis, primarily as a tumor suppressor gene is associated with a variety of different cancers. However, its function in pancreatic cancer remains uncertain. METHODS: SPOP expression and the association between its expression and patient prognosis and immune function were evaluated using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), The Tumor Immune Estimation Resource 2.0 (TIMER2.0) database, cBioportal, and various bioinformatic databases. Enrichment analysis of SPOP and the association between SPOP expression with clinical stage and grade were analyzed using the R software package. Then immunohistochemistry (IHC) was used to estimate the correlation between SPOP and tumor-infiltrating lymphocytes (TILs) in patients with pancreatic cancer. RESULTS: As part of our study, we assessed that SPOP was anomalously expressed in kinds of cancers, associated with clinical stage and outcomes. Meanwhile, SPOP also played a crucial role in the tumor microenvironment (TME). The expression level of SPOP was significantly correlated to tumor-infiltrating immune cells (TICs) in pancreatic cancer. CONCLUSIONS: Our study uncovered the potential corrections in SPOP with TICs, suggesting that SPOP may act as a biomarker for immunotherapy in pancreatic cancer.

Humans↗
PubMed2004

Molecular aspects of disease pathogenesis in the transmissible spongiform encephalopathies.

The transmissible spongiform encephalopathy (TSE) diseases are a group of rare, fatal, and transmissible neurodegenerative diseases that include kuru and Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, transmissible mink encephalopathy (TME), and chronic wasting disease (CWD) in mule deer and elk. Over the last 20 yr, they have gone from a fascinating but relatively obscure group of diseases to one that is a major agricultural and economic problem as well as a threat to human health. The shift in the relative impact of the TSE diseases began in the late 1970s when the United Kingdom altered the process by which animal carcasses were rendered to provide a protein supplement (i.e., meat and bone meal) to sheep, cattle, and other livestock. Several years later a new disease was recognized in the British cattle population. The pathological and immunohistochemical characteristics of the disease clearly placed it among the TSEs. The new disease was named bovine spongiform encephalopathy (BSE) by the scientific community and "mad cow disease" by the less-than-scientific press. At its peak in the UK, several thousand cattle a year were diagnosed with BSE, and millions of cattle were slaughtered. Introduction of the specified offals ban as well as banning the practice of feeding ruminants to other ruminants has led to a drastic decrease in the number of yearly BSE cases in the UK (less than 500 in 2003), and the epidemic is clearly on the wane. However, BSE has now spread throughout the rest of Europe, as well as to Japan, Russia, Canada, and Israel and thus remains a worldwide problem.A primary concern following the identification of BSE in 1985 was that it might cross species barriers to infect humans. Initially, it was thought that transmission of BSE to humans was unlikely, given that humans appeared to be resistant to scrapie, an animal TSE that had been endemic in British sheep for centuries. However, a few years after BSE was first recognized, a previously unknown form of CJD (variant CJD or vCJD) was identified in young people in Great Britain. The hypothesis that vCJD was the consequence of exposure of humans to BSE has now been supported by several different studies, and over 140 cases of vCJD have been confirmed.

Animals↗
PubMed2003

Local recurrence of rectal cancer after total mesorectal excision without preoperative radiotherapy.

BACKGROUND: At this moment, it is still debatable whether all patients with mobile rectal cancer who undergo surgical removal of the tumor should be treated with preoperative radiotherapy, since it is likely that only certain patients will benefit from this strategy. In this study, patients with mobile rectal cancer were immediately operated upon and only those with positive nodes or with incomplete resection received adjuvant radiotherapy. AIMS OF THE STUDY: To investigate the local recurrence rate after the use of a selective policy of adjuvant radiotherapy and to determine risk factors for local recurrence. METHODS: In a 5-yr-period, 178 patients with rectal cancer were referred to our institute. A total of 131 patients with mobile rectal cancer were treated with curative intent, which implied a microscopically radical resection and no signs of distant metastasis at operation. A retrospective analysis was undertaken to investigate the incidence of local recurrence in this curative group and to determine risk factors for local recurrence. RESULTS: The postoperative mortality in the curative group was 5.3%. Local recurrences were observed in 6 patients (4.6%) after a median period of 25 mo (range 11-37); two of them also had distant metastases detected at the same time. The highest local recurrence rates were seen in men (5.3%), in distal rectal cancers (6.9%), and in the node-positive group (8.7%). CONCLUSION: A low local recurrence rate can be achieved after total mesorectal excision (TME) without preoperative radiotherapy. Our results suggest using preoperative radiotherapy only for those patients who are at a higher risk for local recurrence. Staging techniques for selection of these patients are at this moments till inappropriate.

Adult↗
PubMed2026

Proteomic signatures of adipocyte recruitment in breast cancer.

The tumor microenvironment (TME) is increasingly recognized as a dynamic regulator of breast cancer progression, with adipocytes functioning as active contributors rather than passive bystanders. Here, we investigated the proteomic and morphologic reprogramming of breast cancer-associated adipocytes (BrCAAs) in response to triple-negative breast cancer (TNBC). Using conditioned medium from HCC1143 cells, we established an in vitro BrCAA model and performed mass spectrometry-based proteomics. Comparative profiling revealed 256 differentially expressed proteins, enriched for pathways including fatty acid degradation, carbon metabolism, and glycogen turnover, consistent with a metabolic shift from energy storage to energy supply. Gene ontology and protein-protein interaction analyses further identified cytoskeletal remodeling, adhesion dynamics, and secretory pathway activation, supporting BrCAA-driven microenvironmental remodeling. In the MMTV-PyMT mouse model, morphometric analysis demonstrated progressive size reduction and increased contour irregularity of adipocytes adjacent to tumors, correlating with proteomic evidence of metabolic stress. Importantly, BrCAAs localized at tumor interfaces were associated with increased microvessel density and CD105+ endothelial activation compared to desmoplastic zones. Proteomic enrichment highlighted pro-angiogenic remodeling, with validation of basigin (BSG), integrin αV (ITGAV), and 2,4-dienoyl-CoA reductase 1 (DECR1). Collectively, our findings establish BrCAAs as metabolically and structurally reprogrammed stromal components that promote tumor metabolism and localized angiogenesis, representing potential therapeutic targets in aggressive breast cancer.

Female↗
PubMed2003

Transmissible spongiform encephalopathies in non-domestic animals: origin, transmission and risk factors.

The transmissible spongiform encephalopathies (TSEs), scrapie and bovine spongiform encephalopathy (BSE), are serious diseases of domestic animals. Although not as significant in terms of numbers of animals affected or geographical distribution, TSEs also affect non-domestic animals. Transmissible mink encephalopathy (TME) was the first TSE to be identified in non-domestic animals. This disease of captive mink (Mustela vison) is very rare and is associated with exposure through feed contaminated by a TSE agent. The second TSE to be identified in non-domestic animals was chronic wasting disease (CWD) of deer and elk. This disease is not known to be associated with feedstuffs contaminated with the agent of CWD, but the natural route of exposure appears to be oral, possibly through direct interaction between animals or through environmental contamination. Over the last five years, the known distribution of CWD across North America has expanded, increasing concerns over the impact of this disease on populations of free-ranging cervids and the viability of game farming industries. Concurrent with the epidemic of BSE, a variety of non-domestic ruminants and felid species were also affected in the United Kingdom, presumably through exposure to the agent in contaminated feed. These examples illustrate that when non-domestic animals are held in captivity, they depend upon feeds supplied by their caretakers and may show degrees of susceptibility to infectious agents in feeds which vary from those of domestic species. Although humans have less influence over exposure of free-ranging species to infectious agents, monitoring these populations for diseases may be important for managing the health of these animals. It is important to institute or continue surveillance for an entire range of infectious diseases, including TSEs, in free-ranging and captive non-domestic species. Study of diseases in these species may provide important information about infectious agents of concern for domestic animals and humans.

Animals↗
PubMed2005

Prion disease: a deadly disease for protein misfolding.

An infectious particle, termed prion, composed largely and perhaps solely of a single protein, is the likely causative agent of prion disease. It produces lethal decline of cognitive and motor function. The responsible protein arrives at a pathogenic state by misfolding from a normal form that has ubiquitous tissue distribution. Prion diseases are often called spongiform encephalopathies. Probably most mammalian species develop these diseases. Specific examples in various animals are -Scrapie, Transmissible Mink Encephalopathy (TME ), Chronic Wasting Disease(CWD) and bovine spongiform encephalopathy (BSE). Humans are also susceptible to several prion diseases: Creutzfeld-Jacob Disease (CJD), Gerstmann-Straussler-Scheinker Syndrome (GSS), Fatal Familial Insomnia (FFI), Kuru and Alpers Syndrome. This paper reviews transmission of this diseases, protein involvement, nature of protein, the conversion process from PrP(c) to PrP(Sc), conversion of prion protein in vitro, the different proposed models for the conversion of PrP(c) to PrP(Sc), prion and other amyloid diseases, prion strains, structure of PrP(c) the particular process that may induce prion disease, and immunization against these diseases.

Animals↗
PubMed2002

Sphincter and nerve preserving total mesorectal excision.

The summer of 2002 has seen the introduction of two new key words in the literature on rectal carcinoma. The words are TME Workshop. Papers attesting to a major impact on rectal cancer outcomes in Norway, Sweden, and Holland, are the background to two major papers in the August British Journal of Surgery, one from Ireland and one from Sweden plus a leading article from a professor in Singapore entitled "Adjuvant therapy for rectal cancer cannot be based on the results of other surgeons".

Autonomic Pathways↗
PubMed2006

Better surgery and better selection for adjuvants--still the key to improving outcomes in rectal cancer.

UNLABELLED: In reviewing the current issues in rectal cancer management the word specialist recurs again and again. The modern hospital requires consultants with special interest in each of the key stages of decision making: Clinical assessment--usually the surgeon MRI. Fine slice individually orientated phased array coil studies with a specially trained radiologist. CT--now routine for metastases Neo-adjuvant therapy. Special interest in the disease in both clinical and medical oncology is essential. SURGERY: The challenges of the distal pelvis make it increasingly unacceptable for surgeons without a "special interest" to operate on mid and low cancer. Histopathology: The lessons of Professor Quirke have brought the specialised histopathologist out of his laboratory into the cruel role of "surgical auditor"--providing circumferential margin examination plus naked eye, TME quality assessment. This gives us two invaluable measurable short-term goals improving the quality for surgical practice. When a hospital can provide special interest doctors in all these fields and when they co-operate in a constructive manner the modern colorectal MDT can lead the way for the whole field of cancer management. It remains a probability that the use of high definition improved quality video based teaching of surgical technique is the single most effective weapon that we have in our battle against this most challenging of malignanvies.

Humans↗
PubMedDate not supplied

Lusitropic changes induced by acid base alterations in cat papillary muscles.

The present work investigates the effects of acid-base alterations upon myocardial relaxation. Experiments were performed in cat papillary muscles contracting isometrically at constant frequency (0.2 Hz) and temperature (29 degrees C). To induce intracellular alkalosis at constant pH0, 20 mM NH4Cl were added to the perfusate. Alkalosis at variable pH0 was induced by switching from the control solution (5% CO2-95% O2, pH0 7.40) to a solution identical to the control one, equilibrated with 3% CO2-97% O2. Acidosis was induced by switching the control perfusate to a solution equilibrated with 12% CO2-88% O2 in which pH0 was either allowed to change or kept constant by manipulation of bicarbonate concentration. Alkalosis produced a negative lusitropic effect either when pH0 was kept constant or when it was allowed to increase. For an increase in myocardial contractility of 30%, half relaxation tme (T50) and time to peak tension (TTP) were prolonged 9.4 +/- 5% and 5.4 +/- 2% respectively at constant pH0 and 6.8 +/- 0.8 and 4.7 +/- 1% respectively at variable pHo. It is suggested that this negative lusitropic effect of alkalosis can be attributed to an increase in myofilament sensitivity to calcium. Either at constant or at variable pHo acidosis decreased myocardial contractility by approximately 50%. This decrease in contractility was accompanied by a positive lusitropic action only when pHo was allowed to decrease, or when acidosis at constant pHo was evoked in the presence of EIPA, a specific inhibitor of the Na+/H+ exchanger.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1996

Nodal metastasis in the distal mesorectum: need for total mesorectal excision of rectal cancer.

Locoregional failure of rectal cancer is a troublesome problem and a major cause of morbidity and mortality following curative surgery. The mesorectum has been regarded as an important site in local failure after surgery of rectal cancer. Total mesorectal excision (TME) has been raised by some colorectal surgeons to prevent early local recurrence. This study was performed to ascertain the incidence of metastatic lymph nodes in the distal mesorectum (DMR) of the colorectal cancer patient. We also examined the clinicopathologic risk factors of distal mesorectal metastasis. Eight of 53 patients had positive metastatic lymph nodes in DMR. Twenty-seven patients were Dukes B and 26 patients were Dukes C stage. Out of 26 Dukes C patients, 8 patients (30.8%) had metastatic lymph nodes in the DMR. However, there was no significant difference in risk factors between DMR positive and DMR negative patients with Dukes C stage. In conclusion, the incidence of metastatic lymph nodes in DMR was about 30.8%, therefore the mesorectum especially the DMR should be removed completely by total mesorectal excision to eradicate the metastatic lymph nodes which may cause local recurrence.

Aged↗
PubMed2004

Laparoscopic versus conventional open resection of rectal carcinoma: A clinical comparative study.

AIM: To evaluate the feasibility of laparoscopic resection of rectal carcinoma and to compare the short-term outcome of laparoscopic procedure with conventional open surgery for rectal cancer. METHODS: Thirty-eight patients with rectal cancer were included in a prospective non-randomized study. The patients were assigned to laparoscopic (n=18) or open (n=18) colorectal resection. Case selection, surgical technique, and clinical and pathological results were reviewed. RESULTS: The operative time was longer in laparoscopic resection group (LAP) than in open resection group (189+/-18 min vs 146+/-22 min, P<0.05). Intraoperative blood loss and postoperative complications were less in LAP resection group than in open resection group. An earlier return of bowel motility was observed after laparoscopic surgery. The overall postoperative morbidity was 5.6% in the LAP resection group and 27.8% in open resection group (P<0.05). No anastomotic leakage was found in both groups. The pathologic examination showed that the length of the resected specimen, the mean number of harvested lymph nodes in laparoscopic resection group were comparable to those in open resection group. CONCLUSION: Laparoscopic total mesorectal excision (TME) for rectal cancer is a feasible but technically demanding procedure. The present study demonstrates the safety of the procedure, while oncologic results are comparable to the open surgery, with a favorable short-term outcome.

Feasibility Studies↗
PubMed2026

Oxidative Stress Associated LncRNAs as Potential Biomarkers for Prognosis and Immune Responses in Lung Squamous Cell Carcinoma Patients.

Long-chain non-coding RNA (lncRNA) significantly influences lung squamous cell carcinoma's (LUSC) prognostic value and immune infiltration. This study aimed to demonstrate how oxidative stress-related lncRNAs impact lung squamous cell carcinoma (SCC). The Cancer Genome Atlas (TCGA) dataset gathered transcriptome information and related clinical data for LUSC. To build a prognostic model, 10 prognostic-related genes were identified using a series of bioinformatics analyses that compared the OS gene's aberrant expression in tumor and healthy tissues, as well as its association with malignancy. Subjects were stratified into high- and low-risk groups based on the median risk score derived from the 10-gene signature. While the mathematical risk model demonstrated limited independent predictive performance in the validation cohort (AUC ~ 0.5), functional and immunological evaluations revealed significant differences in the tumor microenvironment (TME) across risk strata. Specifically, high-risk patients exhibited distinct immune infiltration profiles and altered immunological scores relative to their low-risk counterparts. Therefore, rather than serving as a direct clinical prediction tool, this oxidative stress-related lncRNA signature provides valuable biological insights into the immune landscape of LUSC and highlights potential therapeutic targets for further mechanistic investigation.

Humans↗
PubMed2026

Integrated Pan-Cancer, Single-Cell, and Spatial Transcriptomic Analyses Identify ZDHHC12 as a Biomarker Associated with Macrophage Infiltration and the Immune Landscape in Glioma.

BACKGROUND: The tumor immune microenvironment (TME) critically influences cancer progression and therapeutic response. However, the pan-cancer expression landscape, prognostic relevance, and spatial distribution of ZDHHC12 remain incompletely characterized. This study investigated the prognostic value of ZDHHC12 and its associations with immune microenvironmental features and drug sensitivity. METHODS: Data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets were used to evaluate ZDHHC12 expression and prognosis across cancer types. Immune infiltration analyses, single-cell RNA sequencing, and spatial transcriptomics were integrated to characterize the associations of ZDHHC12 with the cancer immunity cycle and the spatial architecture of glioma. Drug sensitivity and immunotherapy-related metrics were assessed using pharmacogenomic databases and computational prediction models. RESULTS: ZDHHC12 was aberrantly expressed across multiple tumors and was associated with patient prognosis. Its expression was broadly correlated with immune cell recruitment- and activation-related signatures. In glioma, single-cell and spatial transcriptomic analyses showed enrichment of ZDHHC12 in monocyte/macrophage populations and spatial co-localization with BAK1, CD68, and CD163. ZDHHC12 expression was also associated with predicted drug sensitivity and immunotherapy-related metrics. CONCLUSION: ZDHHC12 may serve as a candidate pan-cancer prognostic biomarker. In glioma, its expression is associated with macrophage-enriched and immunosuppressive microenvironmental features. Functional studies are required to establish causality and determine its therapeutic relevance.

GBM↗
PubMed1999

[Rectum carcinoma. Optimizing therapy by deep resection or excision].

Abdominoperineal excision of the rectum has been the surgical treatment of choice for rectal cancer of the middle and lower third for decades. However, subsequent to technical developments, particularly stapling instruments, sphincter saving procedures such as low anterior or intersphincteric resection superseded abdominoperineal excision in the majority of tumors of the middle and even lower third of the rectum. Within the last seven years (1990-1997), 253 patients with distal rectal cancer underwent surgery--in 204 patients surgery was carried out for the cure of malignancy, whereas in 49 patients surgery was performed for palliation. In the meantime, the rate of abdominoperineal excision with permanent stoma was steadily decreased from 25% (1990-1993) to 9% (1994-1997). Concerning oncologic quality, sphincter saving resections showed evidence that cure rates (3- and 5-year survival) were not compromised by these techniques; conversely, sphincter saving resections offered oncologic cure rates superior to abdominoperineal excision of the rectum. Complete lymphadenectomy with high ligation of the inferior mesenteric artery and total mesorectal excision (TME) are fundamental components of this approach. Moreover, the adverse effects of a permanent colostomy and the consecutively diminished quality of life following abdominoperineal excision can be avoided in approximately 80% of cases. In conclusion, at present 80-85% of rectal carcinomas of the middle or lower third can be surgically treated by sphincter saving low resections without compromising oncologic radicality.

Anastomosis, Surgical↗
PubMed1999

Microvascular network of the healing surface over the temporalis flap in maxillary reconstruction.

This study aims to describe and quantify the microvascular changes of the healing wound in a maxilla reconstructed by a temporalis myofascial flap (TMF). 24 cats underwent partial maxillectomies and reconstruction by TME Vascular infusion was performed immediately following sacrifice and then analyzed by radiography, light and SEM. Results showed that the superficial microvascular layer overlying the TMF underwent a similar transformation as in the histological healing sequence. The vascular density was highest during the initial 6 weeks, followed by reducing density at the chronic inflammatory phase, to normal at the proliferative and remodelling phases. The migrating epithelium brought on a microvascular sub-epithelial plexus, which eventually covered the TMF. The finding that the vascular source of this sub-epithelial plexus comes from the surrounding tissues rather than from the underlying TMF will have surgical implications for bony reconstruction of the maxilla.

Analysis of Variance↗
PubMed1999

Total mesorectal excision with autonomic nerve preservation: a new foundation for the evaluation of multi-disciplinary adjuvant therapy in the management of rectal cancers.

Local and distant recurrence rates and disease-free and overall survival are markedly improved by total mesorectal excision, with little increase in morbidity, compared with other techniques of resection of rectal cancer. Adjuvant therapy is associated with significant morbidity and initial results suggest it may not be beneficial in the aggregate. Adjuvant therapy must be re-evaluated in trials using TME as standard operative technique. Different subgroups of patients, defined by clinical and pathological criteria will be best served by different forms of therapy and should be studied based on rates of local and distant recurrence. Selected groups of patients will be best served by undergoing no adjuvant therapy of any kind.

Chemotherapy, Adjuvant↗
PubMed2000

[Indications for and limitations of low anterior resection].

The indications for low anterior resection are based mainly on tumor location, penetration depth, histology, macroscopic appearance, etc. Patients with tumors located 2 cm above the puborectal muscle by digital examination can undergo low anterior resection. Distal surgical margins should be at least 1 cm from the tumor in cases of differentiated cancer and localized tumors of stage T2 or less and more than 2 cm in poorly differentiated cancer and tumors of stage T3 or greater with total mesorectal excision (TME). Longer distal surgical margins should be provided in patients with unlocalized tumors and extensive node metastasis. The final decision on whether low anterior resection is appropriate should be made after mesorectal preparation down to the levator muscles with adequate surgical margins. Low anterior resection is contraindicated in patients with poor anorectal function and high age. A rectal stump 1 to 2 cm from the dentate line should be maintained for better postoperative anorectal function if radical excision can still be performed.

Digestive System Surgical Procedures↗
PubMed2000

[Results of radiotherapy in rectal carcinoma].

Adjuvant combined radio-chemotherapy in rectal cancer is indicated in stage UICC II and III (pT3/4 and/or pN+) without distant metastases (exception: resectable metastases of the liver). Radiotherapy alone improves local control in the pelvis. A statistical significant improvement of survival is only achievable in combination with systemic chemotherapy. In Germany neo-adjuvant, conventional fractionated radio-chemotherapy over five weeks is applied in patients with surgically inoperable tumors to achieve a "down-staging" with improvement of resectability. Neo-adjuvant radiotherapy of operable rectal cancer in five fractions of high single doses within one week has revealed a statistical significant improvement of survival if compared to surgery alone in the Swedish rectal cancer trial, but is not standard in Germany yet. The influence of technical advances in surgery as total mesorectal excision (TME) on indications of adjuvant therapy is evaluated in prospective randomized studies at this time.

Chemotherapy, Adjuvant↗