Alcohol is an important determinant of the high and fluctuating adult mortality rates in Russia, but cause-specific detail is lacking. Our case-control study investigated the effects of alcohol consumption on male and female cause-specific mortality. In three Russian industrial cities with typical 1990s mortality patterns (Tomsk, Barnaul, Biysk), the addresses of 60,416 residents who had died at ages 15-74 years in 1990-2001 were visited in 2001-05. Family members were present for 50,066 decedents; for 48,557 (97%), the family gave proxy information on the decedents' past alcohol use and on potentially confounding factors. Cases (n=43,082) were those certified as dying from causes we judged beforehand might be substantially affected by alcohol or tobacco; controls were the other 5475 decedents. Case versus control relative risks (RRs; calculated as odds ratios by confounder-adjusted logistic regression) were calculated in ever-drinkers, defining the reference category by two criteria: usual weekly consumption always less than 0.5 half-litre bottles of vodka (or equivalent in total alcohol content) and maximum consumption of spirits in 1 day always less than 0.5 half-litre bottles. Other ever-drinkers were classified by usual weekly consumption into three categories: less than one, one to less than three, and three or more (mean 5.4 [SD 1.4]) bottles of vodka or equivalent. In men, the three causes accounting for the most alcohol-associated deaths were accidents and violence (RR 5.94, 95% CI 5.35-6.59, in the highest consumption category), alcohol poisoning (21.68, 17.94-26.20), and acute ischaemic heart disease other than myocardial infarction (3.04, 2.73-3.39), which includes some misclassified alcohol poisoning. There were significant excesses of upper aerodigestive tract cancer (3.48, 2.84-4.27) and liver cancer (2.11, 1.64-2.70). Another five disease groups had RRs of more than 3.00 in the highest alcohol category: tuberculosis (4.14, 3.44-4.98), pneumonia (3.29, 2.83-3.83), liver disease (6.21, 5.16-7.47), pancreatic disease (6.69, 4.98-9.00), and ill-specified conditions (7.74, 6.48-9.25). Although drinking was less common in women, the RRs associated with it were generally more extreme. After correction for reporting errors, alcohol-associated excesses accounted for 52% of all study deaths at ages 15-54 years (men 8182 [59%] of 13968, women 1565 [33%] of 4751) and 18% of those at 55-74 years (men 3944 [22%] of 17,536, women 1493 [12%] of 12 302). Allowance for under-representation of extreme drinkers would further increase alcohol-associated proportions. Large fluctuations in mortality from these ten strongly alcohol-associated causes were the main determinants of recent fluctuations in overall mortality in the study region and in Russia as a whole. Alcohol-attributable mortality varies by year; in several recent years, alcohol was a cause of more than half of all Russian deaths at ages 15-54 years. Alcohol accounts for most of the large fluctuations in Russian mortality, and alcohol and tobacco account for the large difference in adult mortality between Russia and western Europe. UK Medical Research Council, Cancer Research UK, British Heart Foundation, International Agency for Research on Cancer, and European Commission Directorate-General for Research.

Russian adults have extraordinarily high rates of premature death. Retrospective enquiries to the families of about 50,000 deceased Russians had found excess vodka use among those dying from external causes (accident, suicide, violence) and eight particular disease groupings. We now seek prospective evidence of these associations. In three Russian cities (Barnaul, Byisk, and Tomsk), we interviewed 200,000 adults during 1999-2008 (with 12,000 re-interviewed some years later) and followed them until 2010 for cause-specific mortality. In 151,000 with no previous disease and some follow-up at ages 35-74 years, Poisson regression (adjusted for age at risk, amount smoked, education, and city) was used to calculate the relative risks associating vodka consumption with mortality. We have combined these relative risks with age-specific death rates to get 20-year absolute risks. Among 57,361 male smokers with no previous disease, the estimated 20-year risks of death at ages 35-54 years were 16% (95% CI 15-17) for those who reported consuming less than a bottle of vodka per week at baseline, 20% (18-22) for those consuming 1-2·9 bottles per week, and 35% (31-39) for those consuming three or more bottles per week; trend p<0·0001. The corresponding risks of death at ages 55-74 years were 50% (48-52) for those who reported consuming less than a bottle of vodka per week at baseline, 54% (51-57) for those consuming 1-2·9 bottles per week, and 64% (59-69) for those consuming three or more bottles per week; trend p<0·0001. In both age ranges most of the excess mortality in heavier drinkers was from external causes or the eight disease groupings strongly associated with alcohol in the retrospective enquiries. Self-reported drinking fluctuated; of the men who reported drinking three or more bottles of vodka per week who were reinterviewed a few years later, about half (185 of 321) then reported drinking less than one bottle per week. Such fluctuations must have substantially attenuated the apparent hazards of heavy drinking in this study, yet self-reported vodka use at baseline still strongly predicted risk. Among male non-smokers and among females, self-reported heavy drinking was uncommon, but seemed to involve similar absolute excess risks. This large prospective study strongly reinforces other evidence that vodka is a major cause of the high risk of premature death in Russian adults. UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Union, WHO International Agency for Research on Cancer.

Background The changes in Russian mortality rates during the last two decades are unprecedented in a modern industrialized country. Although these fluctuations have attracted much interest, trends for major groups of causes of death have been analysed while trends in specific causes of death might shed light on the underlying determinants. Methods We analysed trends in total and cause-specific mortality in Russia for 1991–2006. The records of 24 836 forensic autopsies carried out during the period 1990–2004 in the city of Barnaul were analysed with respect to blood alcohol level. Results Diseases of the circulatory system (in the age group 35–69 years) and external causes (in the age group 15–34 years) were the main contributors to the fluctuations in Russian mortality rates observed in 1991–2006. The largest relative changes were for conditions directly related to alcohol intake. Among cardiovascular diseases, fluctuations were due to ‘other forms’ of acute and chronic ischaemia, and to atherosclerotic heart disease, while rates of myocardial infarction were low and relatively constant. In the autopsy series a very high proportion of decedents whose death was attributed to ‘other’ or ‘not classified’ cardiovascular diseases had lethal or potentially lethal concentrations of ethanol in blood. Conclusions The increases in mortality in 1991–94 and in 1998–2003 coincided with economic and societal crisis, while decreases in 1994–98 and 2003–06 correlate with improvement in the economic situation. Excessive alcohol intake is a major cause of premature male Russian mortality, although many alcohol-related deaths are wrongly attributed to diseases of the circulatory system.

Research has shown the role of growth factors in lung cancer angiogenesis. Angiogenesis promotes lung cancer progression by stimulating tumor growth, enhancing tumor invasion, contributing to metastasis, and modifying immune system responses within the tumor microenvironment. As a result, new treatment techniques based on the anti-angiogenic characteristics of compounds have been developed. These compounds selectively block the growth factors themselves, their receptors, or the downstream signaling pathways activated by these growth factors. The EGF and VEGF families are the primary targets in this approach, and several studies are being conducted to propose anti-angiogenic drugs that are increasingly suitable for the treatment of lung cancer, either as monotherapy or as combined therapy. The efficacy of the results are encouraging, but caution must be placed on the higher risk of toxicity, outlining the importance of personalized follow-up in the management of these patients.

Lung cancer is currently the second leading cause of cancer death worldwide. In recent years, checkpoint inhibitor immunotherapy (ICI) has emerged as a new treatment. A better understanding of the tumor microenvironment (TMJ) or the immune system surrounding the tumor is needed. Cytokines are small proteins that carry messages between cells and are known to play an important role in the body’s response to inflammation and infection. Cytokines are important for immunity in lung cancer. They promote tumor growth (oncogenic cytokines) or inhibit tumor growth (anti-tumour cytokines) by controlling signaling pathways for growth, proliferation, metastasis, and apoptosis. The immune system relies heavily on cytokines. They can also be produced in the laboratory for therapeutic use. Cytokine therapy helps the immune system to stop the growth or kill cancer cells. Interleukins and interferons are the two types of cytokines used to treat cancer. This article begins by addressing the role of the TMJ and its components in lung cancer. This review also highlights the functions of various cytokines such as interleukins (IL), transforming growth factor (TGF), and tumor necrosis factor (TNF).

A thorough study of Clear Cell Renal Cell Carcinoma (ccRCC) shows that combining tyrosine kinase inhibitors (TKI) with immune checkpoint inhibitors (ICI) shows promising results in addressing the tumor-promoting influences of abnormal immunological and molecular biomarkers in metastatic Clear Cell Renal Cell Carcinoma (ccRCC). These abnormal biomarkers enhance drug resistance, support tumor growth, and trigger cancer-related genes. Ongoing clinical trials are testing new treatment options that appear more effective than earlier ones. However, more research is needed to confirm their long-term safety use and potential side effects. This study highlights vital molecular and immunological biomarkers associated with drug resistance in Clear Cell Renal Cell Carcinoma (ccRCC). Furthermore, this study identifies a number of promising drug candidates and biomarkers that serve as significant contributors to the enhancement of the overall survival of ccRCC patients. Consequently, this article offers pertinent insights on both recently completed and ongoing clinical trials, recommending further toxicity study for the prolonged use of this treatment strategy for patients with metastatic ccRCC, while equipping researchers with invaluable information for the progression of current treatment strategies.